To see the other types of publications on this topic, follow the link: Phospholipase A2 (sPLA2).
Journal articles on the topic 'Phospholipase A2 (sPLA2)'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Phospholipase A2 (sPLA2).'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Themsche, Céline Van, Michèle Jacob, and Christian Salesse. "Human retinal pigment epithelium secretes a phospholipase A2 and contains two novel intracellular phospholipases A2." Biochemistry and Cell Biology 79, no. 1 (January 1, 2001): 1–10. http://dx.doi.org/10.1139/o00-088.
Full textAbstract:
The sensitivity of different phospholipase A2 (PLA2)-active fractions eluted from cation-exchange chromatography to para-bromophenacylbromide (pBPB), Ca2+-EGTA, DTT, heat, and H2SO4 indicates that human cultured retinal pigment epithelial (hRPE) cells probably contain two different intracellular PLA2 enzymes. Control experiments using "back-and-forth" thin-layer chromatography confirmed that, in our assay conditions, the generation of free fatty acids originated solely from PLA2 activity. Together with immunoblot experiments where no cross-reactivity was observed between the hRPE cytosolic PLA2 enzymes and several antisera directed against secretory PLA2s (sPLA2s) and cytosolic PLA2 (cPLA2), these findings suggest that intracellular hRPE PLA2s are different from well-known sPLA2s, cPLA2, and Ca2+-independent PLA2s. We also report an additional hRPE-PLA2 enzyme that is secreted and that exhibits sensitivity to pBPB, Ca2+-EGTA, DTT, heat, and H2SO4, which is characteristic of sPLA2 enzymes. This approximately 22-kDa PLA2 cross-reacted weakly with an antiserum directed against porcine pancreatic group I sPLA2 but strongly with an antiserum directed against N-terminal residues 1-14 of human synovial group II sPLA2, suggesting that this extracellular enzyme is a member of the sPLA2 class of enzymes. We thus conclude that there are three distinct PLA2 enzymes in cultured hRPE cells, including two novel intracellular PLA2s and a 22-kDa secreted sPLA2 enzyme.Key words: phospholipase A2, retinal pigment epithelium, characterization.
2
Rizzo, Maria Teresa, Elisabeth Nguyen, Marlene Aldo-Benson, and Gerard Lambeau. "Secreted phospholipase A2 induces vascular endothelial cell migration." Blood 96, no. 12 (December 1, 2000): 3809–15. http://dx.doi.org/10.1182/blood.v96.12.3809.
Full textAbstract:
Abstract Secreted phospholipase A2 (sPLA2) regulates a variety of cellular functions. The present investigation was undertaken to elucidate the potential role of sPLA2 in endothelial cell (EC) migration. Bovine aortic endothelial cells (BAECs) exposed to sPLA2 placed in the lower compartment of a modified Boyden chamber displayed increased migration compared to cells exposed to vehicle. The effect of sPLA2 on EC migration was time and dose dependent. Migration of BAECs was observed at 30 minutes, increased over 1 to 2 hours, and declined thereafter. At 2 hours of stimulation, sPLA2 (0.01-2 μmol/L) induced 1.2- to 3-fold increased cell migration compared with media alone. Among the different sPLA2s tested, bee venom, Naja naja, and porcine and human pancreatic PLA2s all evoked a migratory response in ECs. Moreover, human synovial fluid, obtained from patients with arthritis and containing sPLA2 activity, induced EC migration. Migration of ECs was significantly reduced after exposure to a catalytic site mutant of pancreatic sPLA2with decreased lipolytic activity as compared to wild-type sPLA2. Similarly, pretreatment of human synovial fluid withp-bromophenacyl bromide, an irreversible inhibitor of sPLA2, markedly decreased the ability of human synovial fluid to stimulate EC migration. Moreover, migration of ECs was stimulated on exposure to hydrolytic products of sPLA2activity including arachidonic acid, lysophosphatidic acid, and lysophosphatidylcholine. These findings suggest that sPLA2plays a physiologic role in induction of EC migration. Moreover, the effects of sPLA2 on EC migration are mediated, at least in part, by its catalytic activity.
3
Rizzo, Maria Teresa, Elisabeth Nguyen, Marlene Aldo-Benson, and Gerard Lambeau. "Secreted phospholipase A2 induces vascular endothelial cell migration." Blood 96, no. 12 (December 1, 2000): 3809–15. http://dx.doi.org/10.1182/blood.v96.12.3809.h8003809_3809_3815.
Full textAbstract:
Secreted phospholipase A2 (sPLA2) regulates a variety of cellular functions. The present investigation was undertaken to elucidate the potential role of sPLA2 in endothelial cell (EC) migration. Bovine aortic endothelial cells (BAECs) exposed to sPLA2 placed in the lower compartment of a modified Boyden chamber displayed increased migration compared to cells exposed to vehicle. The effect of sPLA2 on EC migration was time and dose dependent. Migration of BAECs was observed at 30 minutes, increased over 1 to 2 hours, and declined thereafter. At 2 hours of stimulation, sPLA2 (0.01-2 μmol/L) induced 1.2- to 3-fold increased cell migration compared with media alone. Among the different sPLA2s tested, bee venom, Naja naja, and porcine and human pancreatic PLA2s all evoked a migratory response in ECs. Moreover, human synovial fluid, obtained from patients with arthritis and containing sPLA2 activity, induced EC migration. Migration of ECs was significantly reduced after exposure to a catalytic site mutant of pancreatic sPLA2with decreased lipolytic activity as compared to wild-type sPLA2. Similarly, pretreatment of human synovial fluid withp-bromophenacyl bromide, an irreversible inhibitor of sPLA2, markedly decreased the ability of human synovial fluid to stimulate EC migration. Moreover, migration of ECs was stimulated on exposure to hydrolytic products of sPLA2activity including arachidonic acid, lysophosphatidic acid, and lysophosphatidylcholine. These findings suggest that sPLA2plays a physiologic role in induction of EC migration. Moreover, the effects of sPLA2 on EC migration are mediated, at least in part, by its catalytic activity.
4
Shridas, Preetha, and Nancy R. Webb. "Diverse Functions of Secretory Phospholipases A2." Advances in Vascular Medicine 2014 (July 15, 2014): 1–11. http://dx.doi.org/10.1155/2014/689815.
Full textAbstract:
Phospholipase A2 enzymes (PLA2s) catalyze the hydrolysis of glycerophospholipids at their sn-2 position releasing free fatty acids and lysophospholipids. Mammalian PLA2s are classified into several categories of which important groups include secreted PLA2s (sPLA2s) and cytosolic PLA2s (cPLA2s) that are calcium-dependent for their catalytic activity and calcium-independent cytosolic PLA2s (iPLA2s). Platelet-activating factor acetylhydrolases (PAF-AHs), lysosomal PLA2s, and adipose-specific PLA2 also belong to the class of PLA2s. Generally, cPLA2 enzymes are believed to play a major role in the metabolism of arachidonic acid, the iPLA2 family to membrane homeostasis and energy metabolism, and the sPLA2 family to various biological processes. The focus of this review is on recent research developments in the sPLA2 field. sPLA2s are secreted enzymes with low molecular weight (with the exception of GIII sPLA2), Ca2+-requiring enzymes with a His-Asp catalytic dyad. Ten enzymatically active sPLA2s and one devoid of enzymatic activity have been identified in mammals. Some of these sPLA2s are potent in arachidonic acid release from cellular phospholipids for the biosynthesis of eicosanoids, especially during inflammation. Individual sPLA2 enzymes exhibit unique tissue and cellular localizations and specific enzymatic properties, suggesting their distinct biological roles. Recent studies indicate that sPLA2s are involved in diverse pathophysiological functions and for most part act nonredundantly.
5
Wei, Yulong, Lesan Yan, Lijun Luo, Tao Gui, Bian Jang, Ahmad Amirshaghaghi, Tianyan You, Andrew Tsourkas, Ling Qin, and Zhiliang Cheng. "Phospholipase A2 inhibitor–loaded micellar nanoparticles attenuate inflammation and mitigate osteoarthritis progression." Science Advances 7, no. 15 (April 2021): eabe6374. http://dx.doi.org/10.1126/sciadv.abe6374.
Full textAbstract:
Treating osteoarthritis (OA) remains a major clinical challenge. Despite recent advances in drug discovery and development, no disease-modifying drug for knee OA has emerged with any notable clinical success, in part, due to the lack of valid and responsive therapeutic targets and poor drug delivery within knee joints. In this work, we show that the amount of secretory phospholipase A2 (sPLA2) enzyme increases in the articular cartilage in human and mouse OA cartilage tissues. We hypothesize that the inhibition of sPLA2 activity may be an effective treatment strategy for OA. To develop an sPLA2-responsive and nanoparticle (NP)–based interventional platform for OA management, we incorporated an sPLA2 inhibitor (sPLA2i) into the phospholipid membrane of micelles. The engineered sPLA2i-loaded micellar NPs (sPLA2i-NPs) were able to penetrate deep into the cartilage matrix, prolong retention in the joint space, and mitigate OA progression. These findings suggest that sPLA2i-NPs can be promising therapeutic agents for OA treatment.
6
Taketomi, Yoshitaka, Yoshimi Miki, and Makoto Murakami. "Old but New: Group IIA Phospholipase A2 as a Modulator of Gut Microbiota." Metabolites 12, no. 4 (April 14, 2022): 352. http://dx.doi.org/10.3390/metabo12040352.
Full textAbstract:
Among the phospholipase A2 (PLA2) superfamily, the secreted PLA2 (sPLA2) family contains 11 mammalian isoforms that exhibit unique tissue or cellular distributions and enzymatic properties. Current studies using sPLA2-deficient or -overexpressed mouse strains, along with mass spectrometric lipidomics to determine sPLA2-driven lipid pathways, have revealed the diverse pathophysiological roles of sPLA2s in various biological events. In general, individual sPLA2s exert their specific functions within tissue microenvironments, where they are intrinsically expressed through hydrolysis of extracellular phospholipids. Recent studies have uncovered a new aspect of group IIA sPLA2 (sPLA2-IIA), a prototypic sPLA2 with the oldest research history among the mammalian PLA2s, as a modulator of the gut microbiota. In the intestine, Paneth cell-derived sPLA2-IIA acts as an antimicrobial protein to shape the gut microbiota, thereby secondarily affecting inflammation, allergy, and cancer in proximal and distal tissues. Knockout of intestinal sPLA2-IIA in BALB/c mice leads to alterations in skin cancer, psoriasis, and anaphylaxis, while overexpression of sPLA2-IIA in Pla2g2a-null C57BL/6 mice induces systemic inflammation and exacerbates arthritis. These phenotypes are associated with notable changes in gut microbiota and fecal metabolites, are variable in different animal facilities, and are abrogated after antibiotic treatment, co-housing, or fecal transfer. These studies open a new mechanistic action of this old sPLA2 and add the sPLA2 family to the growing list of endogenous factors capable of affecting the microbe–host interaction and thereby systemic homeostasis and diseases.
7
Hite, R. Duncan, Michael C. Seeds, Randy B. Jacinto, R. Balasubramanian, Moseley Waite, and David Bass. "Hydrolysis of surfactant-associated phosphatidylcholine by mammalian secretory phospholipases A2." American Journal of Physiology-Lung Cellular and Molecular Physiology 275, no. 4 (October 1, 1998): L740—L747. http://dx.doi.org/10.1152/ajplung.1998.275.4.l740.
Full textAbstract:
Hydrolysis of surfactant-associated phospholipids by secretory phospholipases A2 is an important potential mechanism for surfactant dysfunction in inflammatory lung diseases. In these conditions, airway secretory phospholipase A2(sPLA2) activity is increased, but the type of sPLA2 and its impact on surfactant function are not well understood. We examined in vitro the effect of multiple secretory phospholipases A2 on surfactant, including their ability to 1) release free fatty acids, 2) release lysophospholipids, and 3) increase the minimum surface tension (γmin) on a pulsating bubble surfactometer. Natural porcine surfactant and Survanta were exposed to mammalian group I (recombinant porcine pancreatic) and group II (recombinant human) secretory phospholipases A2. Our results demonstrate that mammalian group I sPLA2 hydrolyzes phosphatidylcholine (PC), producing free fatty acids and lysophosphatidylcholine, and increases γmin. In contrast, mammalian group II sPLA2 demonstrates limited hydrolysis of PC and does not increase γmin. Group I and group II secretory phospholipases A2 from snake venom hydrolyze PC and inhibit surfactant function. In summary, mammalian secretory phospholipases A2 from groups I and II differ significantly from each other and from snake venom in their ability to hydrolyze surfactant-associated PC.
8
Krizaj, Igor. "Roles of Secreted Phospholipases A2 in the Mammalian Immune System." Protein & Peptide Letters 21, no. 12 (November 5, 2014): 1201–8. http://dx.doi.org/10.2174/0929866521666140819122624.
Full textAbstract:
Secreted phospholipase A2 (sPLA2) molecules constitute a family of proteins that are involved functionally in many biological processes. In particular, they participate in diverse pathophysiological settings as enzymes that release free fatty acids and lysophospholipids from phospholipids in biological membranes, or as ligands for various cellular receptors. In this review the confirmed or expected functions of sPLA2s in the mammalian immune system are surveyed. Some of the twelve mammalian sPLA2 molecules constitute part of the so-called innate immune system by virtue of their antibacterial, antiviral and antifungal activities. They are also involved in acute inflammation, a protective reaction of the body to infection or injury. The acute inflammation sometimes escapes regulation, becomes chronic and can evolve into a severe pathology. One or more types of sPLA2 are involved in asthma, rheumatoid arthritis, sepsis, atherosclerosis, myocardial infarction, Crohn’s disease, ulcerative colitis and cancer. sPLA2s are thus important therapeutic targets as well as biotherapeutic molecules. Improving the selectivity of inhibitors of sPLA2s to be able to target a particular sPLA2 could therefore be one of the most important tasks for future research.
9
Wong, Dennis A., Yoshihiro Kita, Naonori Uozumi, and Takao Shimizu. "Discrete Role for Cytosolic Phospholipase A2α in Platelets." Journal of Experimental Medicine 196, no. 3 (July 29, 2002): 349–57. http://dx.doi.org/10.1084/jem.20011443.
Full textAbstract:
Among several different types of phospholipase A2 (PLA2), cytosolic PLA2 (cPLA2)α and group IIA (IIA) secretory PLA2 (sPLA2) have been studied intensively. To determine the discrete roles of cPLA2α in platelets, we generated two sets of genetically engineered mice (cPLA2α−/−/sPLA2-IIA−/− and cPLA2α−/−/sPLA2-IIA+/+) and compared their platelet function with their respective wild-type C57BL/6J mice (cPLA2α+/+/sPLA2-IIA−/−) and C3H/HeN (cPLA2α+/+/sPLA2-IIA+/+). We found that cPLA2α is needed for the production of the vast majority of thromboxane (TX)A2 with collagen stimulation of platelets. In cPLA2α-deficient mice, however, platelet aggregation in vitro is only fractionally decreased because small amounts of TX produced by redundant phospholipase enzymes sufficiently preserve aggregation. In comparison, adenosine triphosphate activation of platelets appears wholly independent of cPLA2α and sPLA2-IIA for aggregation or the production of TX, indicating that these phospholipases are specifically linked to collagen receptors. However, the lack of high levels of TX limiting vasoconstriction explains the in vivo effects seen: increased bleeding times and protection from thromboembolism. Thus, cPLA2α plays a discrete role in the collagen-stimulated production of TX and its inhibition has a therapeutic potential against thromboembolism, with potentially limited bleeding expected.
10
Hite, R. Duncan, Michael C. Seeds, Anca M. Safta, Randolph B. Jacinto, Julianna I. Gyves, David A. Bass, and B. Moseley Waite. "Lysophospholipid generation and phosphatidylglycerol depletion in phospholipase A2-mediated surfactant dysfunction." American Journal of Physiology-Lung Cellular and Molecular Physiology 288, no. 4 (April 2005): L618—L624. http://dx.doi.org/10.1152/ajplung.00274.2004.
Full textAbstract:
Pulmonary surfactant's complex mixture of phospholipids and proteins reduces the work of breathing by lowering alveolar surface tension during respiration. One mechanism of surfactant damage appears to be the hydrolysis of phospholipid by phospholipases activated in the inflamed lung. Humans have several candidate secretory phospholipase A2 (sPLA2) enzymes in lung cells and infiltrating leukocytes that could damage extracellular surfactant. We considered two mechanisms of surfactant disruption by five human sPLA2s, including generation of lysophospholipids and the depletion of specific phospholipids. All five sPLA2s studied ultimately caused surfactant dysfunction. Each enzyme exhibited a different pattern of hydrolysis of surfactant phospholipids. Phosphatidylcholine, the major phospholipid in surfactant and the greatest potential source for generation of lysophospholipids, was susceptible to hydrolysis by group IB, group V, and group X sPLA2s, but not group IIA or IID. Group IIA hydrolyzed both phosphatidylethanolamine and phosphatidylglycerol, whereas group IID was active against only phosphatidylglycerol. Thus, with groups IB and X, the generation of lysophospholipids corresponded with surfactant dysfunction. However, hydrolysis of and depletion of phosphatidylglycerol had a greater correlation with surfactant dysfunction for groups IIA and IID. Surfactant dysfunction caused by group V sPLA2 is less clear and may be the combined result of both mechanisms.
11
Sato, Hiroyasu, Yoshitaka Taketomi, Yuki Isogai, Seiko Masuda, Tetsuyuki Kobayashi, Kei Yamamoto, and Makoto Murakami. "Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation." Biochemical Journal 421, no. 1 (June 12, 2009): 17–27. http://dx.doi.org/10.1042/bj20082429.
Full textAbstract:
PLA2 (phospholipase A2) group III is an atypical sPLA2 (secretory PLA2) that is homologous with bee venom PLA2 rather than with other mammalian sPLA2s. In the present paper, we show that endogenous group III sPLA2 (PLA2G3) is expressed in mouse skin and that Tg (transgenic) mice overexpressing human PLA2G3 spontaneously develop skin inflammation. Pla2g3-Tg mice over 9 months of age frequently developed dermatitis with hyperkeratosis, acanthosis, parakeratosis, erosion, ulcer and sebaceous gland hyperplasia. The dermatitis was accompanied by infiltration of neutrophils and macrophages and by elevated levels of pro-inflammatory cytokines, chemokines and prostaglandin E2. In addition, Pla2g3-Tg mice had increased lymph aggregates and mucus in the airway, lymphocytic sialadenitis, hepatic extramedullary haemopoiesis, splenomegaly with increased populations of granulocytes and monocytes/macrophages, and increased serum IgG1. Collectively, these observations provide the first demonstration of spontaneous development of inflammation in mice with Tg overexpression of mammalian sPLA2.
12
K, Endang Retnowati, Wiyanda Hidayati S, and Liana . "AKTIVITAS FOSFOLIPASE-A2 SEKRETORIS PLASMA TROMBOSITOPENIA DEMAM BERDARAH DENGUE." INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY 17, no. 1 (March 26, 2018): 12. http://dx.doi.org/10.24293/ijcpml.v17i1.1042.
Full textAbstract:
Infected macrophages by dengue virus will produce phospholipase-A2 (PLA2) enzyme, that can promote arachidonic acidmetabolism that produce inflammatory mediators, causing endhothelial damage and severe plasma leakage. Capillary endothelialdamage can cause platelet adhesion and aggregation, so that many platelets will be consumed. The role of sPLA2 (secretoryphospholipase-A2), which is a part of PLA2 in dengue and thrombocytopenia up to now has not been widely studied. The objective ofthe study is to analyze the association between the activity of plasma secretory phospholipase-A2 and the degree of thrombocytopeniain DHF adult patients. the study is carried out by a cross sectional, observational analytical study on 45 hospitalized adult patientssuffering dengue hemorrhagic fever in the Tropical Infection Ward, Department of Internal Medicine, Dr. Soetomo Hospital Surabaya,which has been conducted from February–December 2009. The diagnosis of Dengue Haemorrhagic Fever (DHF) was based on the1997 World Health Organization (WHO) criteria, that minimally had one positive serology marker of dengue. Venous blood wastaken from the patient for examining the activity of secretory phospholipase-A2 by correlated enzyme assay method, and plateletcount using automated hematology analyzer. The results of the secretory phospholipase-A2 activity and degree of thrombocytopeniawere analyzed by Pearson correlation test to determine the correlation between the two variables. In this study so far was foundthat the secretory phospholipase-A2 activity in DHF patients was 36.9–195.6 unit/mL (mean 97.49 unit/mL, SD 30.06 unit/mL).The mean of secretory phospholipase-A2 activity was increased according to the degree of thrombocytopenia severity. The mean ofsecretory phospholipase-A2 activities were 91.65 unit/mL, 98.94 unit/mL, and 110.47 unit/mL. The degree of thrombocytopeniawas divided into mild, moderate, and severe. Most of the patients showed mild thrombocytopenia. The sPLA2 activity in this studywas increased in DHF patients with second day of fever, and then decreased at the third and forth day of fever, and increased inDBD patients suffering fifth day of fever. The statistical analyzes show a non significant correlation between secretory phospholipaseA2 activity and degree of thrombocytopenia (p = 0.579). This result may be caused by several factors which influencing thethrombocytopenia in DHF, such as bone marrow suppression, dengue viral serotype, influence of cytosolic phospholipase-A2 (cPLA2)activity, and other proinflammatory cytokines which in this study could not be controlled. Statistical analyzes show a significantcorrelation between sPLA2 activity and the day of fever (p = 0.04). Further studies should have to be carried out in order to knowthe pattern of sPLA2 activity in DHF grade I, II, III, and IV, and to know the influence of other proinflammatory cytokines and viralserotypes in sPLA2 activities.
13
Ramoner, Reinhold, Thomas Putz, Hubert Gander, Andrea Rahm, Georg Bartsch, Claudia Schaber, and Martin Thurnher. "Dendritic-cell activation by secretory phospholipase A2." Blood 105, no. 9 (May 1, 2005): 3583–87. http://dx.doi.org/10.1182/blood-2004-08-3001.
Full textAbstract:
Abstract Dendritic cells (DCs), also referred to as the sentinels of the immune system, induce and coordinate important functions of immune surveillance. DCs acquire immunity-initiating capacity only after a process of maturation usually induced by ligands that bind to members of the tumor necrosis factor (TNF) or toll-like receptor families. Secretory phospholipase A2 (sPLA2), which hydrolyzes the sn-2 ester bond of glycerophospholipids, regulates a variety of cellular functions including migration of endothelial cells and neurite outgrowth. In the present study we investigated the role of sPLA2 in DC biology. We report that human monocyte-derived DC cultures lack sPLA2 activity but respond to exogenous sPLA2. sPLA2 alone and in cooperation with TNF-α and interleukin 1 β (IL-1β) induced fatty acid release from DC membranes, which was accompanied by upregulation of surface markers and by an increase in the migratory and immunostimulatory capacity of the DCs. Our findings indicate that secreted enzymes such as sPLA2 can contribute to DC maturation and emphasize the role of lipid mediators in the regulation of immune responses. This observation may also have implications for DC-based vaccine development.
14
Muñoz-Sanjuán, Ignacio, and Ali H. Brivanlou. "Induction of Ectopic Olfactory Structures and Bone Morphogenetic Protein Inhibition by Rossy, a Group XII Secreted Phospholipase A2." Molecular and Cellular Biology 25, no. 9 (May 1, 2005): 3608–19. http://dx.doi.org/10.1128/mcb.25.9.3608-3619.2005.
Full textAbstract:
ABSTRACT The secreted phospholipases A2 (sPLA2s) comprise a family of small secreted proteins with the ability to catalyze the generation of bioactive lipids through glycophospholipid hydrolysis. Recently, a large number of receptor proteins and extracellular binding partners for the sPLA2s have been identified, suggesting that these secreted factors might exert a subset of their broad spectrum of biological activities independently of their enzymatic activity. Here, we describe an activity for the sPLA2 group XII (sPLA2-gXII) gene during Xenopus laevis early development. In the ectoderm, sPLA2-gXII acts as a neural inducer by blocking bone morphogenetic protein (BMP) signaling. Gain of function in embryos leads to ectopic neurogenesis and to the specification of ectopic olfactory sensory structures, including olfactory bulb and sensory epithelia. This activity is conserved in the Drosophila melanogaster, Xenopus, and mammalian orthologs and appears to be independent of the lipid hydrolytic activity. Because of its effect on olfactory neurogenesis, we have renamed this gene Rossy, in homage to the Spanish actress Rossy de Palma. We present evidence that Rossy/sPLA2-gXII can inhibit the transcriptional activation of BMP direct-target gene reporters in Xenopus and mouse P19 embryonic carcinoma cells through the loss of DNA-binding activity of activated Smad1/4 complexes. Collectively, these data represent the first evidence for signaling cross talk between a secreted phospholipase A2 and the BMP/transforming growth factor β pathways and identify Rossy/sPLA2-gXII as the only factor thus far described which is sufficient to induce anterior sensory neural structures during vertebrate development.
15
NAKASHIMA, Satoru, Yutaka IKENO, Tatsuya YOKOYAMA, Masakazu KUWANA, Angelo BOLCHI, Simone OTTONELLO, Katsuhiko KITAMOTO, and Manabu ARIOKA. "Secretory phospholipases A2 induce neurite outgrowth in PC12 cells." Biochemical Journal 376, no. 3 (December 15, 2003): 655–66. http://dx.doi.org/10.1042/bj20030830.
Full textAbstract:
sPLA2s (secretory phospholipases A2) belong to a broad and structurally diverse family of enzymes that hydrolyse the sn-2 ester bond of glycerophospholipids. We previously showed that a secreted fungal 15 kDa protein, named p15, as well as its orthologue from Streptomyces coelicolor (named Scp15) induce neurite outgrowth in PC12 cells at nanomolar concentrations. We report here that both p15 and Scp15 are members of a newly identified group of fungal/bacterial sPLA2s. The phospholipid-hydrolysing activity of p15 is absolutely required for neurite outgrowth induction. Mutants with a reduced PLA2 activity exhibited a comparable reduction in neurite-inducing activity, and the ability to induce neurites closely matched the capacity of various p15 forms to promote fatty acid release from live PC12 cells. A structurally divergent member of the sPLA2 family, bee venom sPLA2, also induced neurites in a phospholipase activity-dependent manner, and the same effect was elicited by mouse group V and X sPLA2s, but not by group IB and IIA sPLA2s. Lysophosphatidylcholine, but not other lysophospholipids, nor arachidonic acid, elicited neurite outgrowth in an L-type Ca2+ channel activity-dependent manner. In addition, p15-induced neuritogenesis was unaffected by various inhibitors that block arachidonic acid conversion into bioactive eicosanoids. Altogether, these results delineate a novel, Ca2+- and lysophosphatidylcholine-dependent neurotrophin-like role of sPLA2s in the nervous system.
16
Urazov, S. P., A. N. Chernov, A. V. Cherkas, A. V. Boikov, O. S. Glotov, S. V. Apalko, N. N. Sushentseva, I. A. Polkovnikova, V. V. Smirnov, and S. G. Shcherbak. "Secretory phospholipase A2: a biomarker of inflammation in autoimmune, bacterial and viral diseases." Medical Immunology (Russia) 24, no. 4 (July 13, 2022): 705–28. http://dx.doi.org/10.15789/1563-0625-spa-2460.
Full textAbstract:
Secretory phospholipases A2 (sPLA2) represent a large superfamily of enzymes with a molecular weight of 14-19 kDa, including 15 groups and more than 30 isoforms belonging to four types: secretory (sPLA2), cytosolic (cPLA2), calcium-independent (iPLA2) and lipoprotein-associated phospholipase A2 (LP-PLA2, PAF-AH). Eleven species of secretory sPLA2s (IB, IIA, IIC, IID, IIE, IIF, III, V, X, XIIA, and XIIB) have been found in mammals, performing versatile functions and participating in the pathogenesis of a wide range of diseases. On the one hand, sPLA2 may promote elimination of damaged, apoptotic cells by hydrolyzing membrane phospholipids, and exerts a strong bactericidal and antiviral properties, including pronounced effects against antibiotic-resistant strains of microorganisms. In this regard, the use of sPLA2 may represent a new strategy for the treatment of bacterial and viral infections. Moreover, due to the action of sPLA2 on its substrates, a number of biologically active molecules (arachidonic, lysophosphatidic acids, lysophospholipids, fatty acids, prostaglandins, leukotrienes, thromboxanes) are formed, which provide strong inflammatory, detergent, coagulating effects and increase vascular permeability. This pro-inflammatory role of sPLA2 may explain its increase levels and activity in cardiovascular, respiratory, autoimmune, metabolic, oncological, bacterial and viral disorders. The review article presents a classification of sPLA2 isoforms, their substrates, regulatory factors, biological significance, and mechanisms of their strong bactericidal, virucidal, and pro-inflammatory activity in the heart and lung disorders, autoimmune, metabolic, bacterial, and viral diseases. In particular, the mechanisms of the selective action of sPLA2 against Gram-positive and Gram-negative microorganisms are discussed. We consider diagnostic and prognostic significance, correlations between elevated levels and activity of sPLA2 and distinct clinical symptoms, severity and outcome in the patients with coronary heart disease (CAD), acute myocardial infarction (AMI), atherosclerosis, acute inflammatory lung injury (ALI), respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, bronchial asthma, bacterial infections, septicemia and viral (COVID-19) infections. The opportunity of using sPLA2 as a biomarker of the severity and outcome of patients with chronic obstructive pulmonary disease, bacterial infections, sepsis and viral infections, including COVID-19, is also considered.
17
Christerson, Ulrika, Åsa V. Keita, Martin E. Winberg, Johan D. Söderholm, and Christina Gustafson-Svärd. "Possible Involvement of Intracellular Calcium-Independent Phospholipase A2 in the Release of Secretory Phospholipases from Mast Cells—Increased Expression in Ileal Mast Cells of Crohn’s Disease." Cells 8, no. 7 (July 3, 2019): 672. http://dx.doi.org/10.3390/cells8070672.
Full textAbstract:
Increased activity of secretory phospholipases A2 (sPLA2) type-II was previously observed in ileum of Crohn’s disease (CD). Our aims were to explore the involvement of calcium-independent (i)PLA2β in the release of sPLA2s from the human mast cell (MC) line (HMC-1) and investigate expressions of cytosolic (c)PLA2α, iPLA2β, sPLA2-IIA and sPLA2-V in MCs of CD ileum. The release of sPLA2 was investigated in HMC-1 by immunocytochemistry and ELISA. The expression intensities of PLA2s in mucosal MCs, and the proportion of PLA2-positive MCs, were investigated in normal ileum and in ileum from patients with CD by immunohistochemistry. The calcium ionophore-stimulated release of sPLA2-IIA and sPLA2-V from HMC-1 was reduced by the iPLA2-inhibitor bromoenol lactone. All four PLA2s were detectable in mucosal MCs, both in normal ileum and in CD, but the proportion of iPLA2β-containing mucosal MCs and the expression intensity of sPLA2-IIA was increased in CD. Results indicate that iPLA2β is involved in the secretion of sPLA2s from HMC-1, and suggest that iPLA2β-mediated release of sPLA2 from intestinal MCs may contribute to CD pathophysiology. Ex vivo studies on isolated mucosal mast cells are however needed to clarify the precise role of MC PLA2s in the inflammatory processes of CD.
18
POLGÁR, János, Ruth M. KRAMER, Suzane L. UM, Joseph A. JAKUBOWSKI, and Kenneth J. CLEMETSON. "Human group II 14 kDa phospholipase A2 activates human platelets." Biochemical Journal 327, no. 1 (October 1, 1997): 259–65. http://dx.doi.org/10.1042/bj3270259.
Full textAbstract:
Recombinant human group II phospholipase A2 (sPLA2) added to human platelets in the low μg/ml range induced platelet activation, as demonstrated by measurement of platelet aggregation, thromboxane A2 generation and influx of intracellular free Ca2+ concentration and by detection of time-dependent tyrosine phosphorylation of platelet proteins. The presence of Ca2+ at low millimolar concentrations is a prerequisite for the activation of platelets by sPLA2. Mg2+ cannot replace Ca2+. Mg2+, given in addition to the necessary Ca2+, inhibits sPLA2-induced platelet activation. Pre-exposure to sPLA2 completely blocked the aggregating effect of a second dose of sPLA2. Albumin or indomethacin inhibited sPLA2-induced aggregation, similarly to the inhibition of arachidonic acid-induced aggregation. Platelets pre-treated with heparitinase or phosphatidylinositol-specific phospholipase C lost their ability to aggregate in response to sPLA2, although they still responded to other agonists. This suggests that a glycophosphatidylinositol-anchored platelet-membrane heparan sulphate proteoglycan is the binding site for sPLA2 on platelets. Previous reports have stated that sPLA2 is unable to activate platelets. The inhibitory effect of albumin and Mg2+, frequently used in aggregation studies, and the fact that isolated platelets lose their responsiveness to sPLA2 relatively quickly, may explain why the platelet-activating effects of sPLA2 have not been reported earlier.
19
Masuda, Seiko, Kei Yamamoto, Tetsuya Hirabayashi, Yukio Ishikawa, Toshiharu Ishii, Ichiro Kudo, and Makoto Murakami. "Human group III secreted phospholipase A2 promotes neuronal outgrowth and survival." Biochemical Journal 409, no. 2 (December 21, 2007): 429–38. http://dx.doi.org/10.1042/bj20070844.
Full textAbstract:
Human sPLA2-III [group III secreted PLA2 (phospholipase A2)] is an atypical sPLA2 isoenzyme that consists of a central group III sPLA2 domain flanked by unique N- and C-terminal domains. In the present study, we found that sPLA2-III is expressed in neuronal cells, such as peripheral neuronal fibres, spinal DRG (dorsal root ganglia) neurons and cerebellar Purkinje cells. Adenoviral expression of sPLA2-III in PC12 cells (pheochromocytoma cells) or DRG explants facilitated neurite outgrowth, whereas expression of a catalytically inactive sPLA2-III mutant or use of sPLA2-III-directed siRNA (small interfering RNA) reduced NGF (nerve growth factor)-induced neuritogenesis. sPLA2-III also suppressed neuronal death induced by NGF deprivation. Lipid MS revealed that sPLA2-III overexpression increased the cellular level of lysophosphatidylcholine, a PLA2 reaction product with neuritogenic and neurotropic activities, whereas siRNA knockdown reduced the level of lysophosphatidylcholine. These observations suggest the potential contribution of sPLA2-III to neuronal differentiation and its function under certain conditions.
20
Lee, In-Chul, Dae Yong Kim, and Jong-Sup Bae. "Inhibitory Effect of Zingerone on Secretory Group IIA Phospholipase A2." Natural Product Communications 12, no. 6 (June 2017): 1934578X1701200. http://dx.doi.org/10.1177/1934578x1701200624.
Full textAbstract:
The expression of secretory group IIA phospholipase A2 (sPLA2-IIA) has been shown to be elevated in various inflammatory diseases, and lipopolysaccharide (LPS) up-regulates the expression of sPLA2-IIA in human umbilical vein endothelial cells (HUVECs). Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to have various pharmacological activities. Here, we examined the effects of ZRG on the expression and activity of sPLA2-IIA in LPS-activated HUVECs and in mouse models of endotoxemia and sepsis. Treatment of cells or mice with ZRG inhibited LPS-induced expression and activity of sPLA2-IIA. In addition, ZRG suppressed LPS-mediated activation of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK) 1/2. These results suggest that ZRG inhibits LPS-mediated activation of sPLA2-IIA expression by suppressing cPLA2 and ERK 1/2.
21
Henderson, William R., Emil Y. Chi, James G. Bollinger, Ying-tzang Tien, Xin Ye, Luca Castelli, Yuri P. Rubtsov, et al. "Importance of group X–secreted phospholipase A2 in allergen-induced airway inflammation and remodeling in a mouse asthma model." Journal of Experimental Medicine 204, no. 4 (April 2, 2007): 865–77. http://dx.doi.org/10.1084/jem.20070029.
Full textAbstract:
Arachidonic acid metabolites, the eicosanoids, are key mediators of allergen-induced airway inflammation and remodeling in asthma. The availability of free arachidonate in cells for subsequent eicosanoid biosynthesis is controlled by phospholipase A2s (PLA2s), most notably cytosolic PLA2-α. 10 secreted PLA2s (sPLA2s) have also been identified, but their function in eicosanoid generation is poorly understood. We investigated the role of group X sPLA2 (sPLA2-X), the sPLA2 with the highest in vitro cellular phospholipolysis activity, in acute and chronic mouse asthma models in vivo. The lungs of sPLA2-X−/− mice, compared with those of sPLA2-X+/+ littermates, had significant reduction in ovalbumin-induced infiltration by CD4+ and CD8+ T cells and eosinophils, goblet cell metaplasia, smooth muscle cell layer thickening, subepithelial fibrosis, and levels of T helper type 2 cell cytokines and eicosanoids. These data direct attention to sPLA2-X as a novel therapeutic target for asthma.
22
Mitsuishi, Michiko, Seiko Masuda, Ichiro Kudo, and Makoto Murakami. "Group V and X secretory phospholipase A2 prevents adenoviral infection in mammalian cells." Biochemical Journal 393, no. 1 (December 12, 2005): 97–106. http://dx.doi.org/10.1042/bj20050781.
Full textAbstract:
sPLA2 (secretory phospholipase A2) enzymes have been implicated in various biological events, yet their precise physiological functions remain largely unresolved. In the present study we show that group V and X sPLA2s, which are two potent plasma membrane-acting sPLA2s, are capable of preventing host cells from being infected with an adenovirus. Bronchial epithelial cells and lung fibroblasts pre-expressing group V and X sPLA2s showed marked resistance to adenovirus-mediated gene delivery in a manner dependent on their catalytic activity. Although adenovirus particles were insensitive to recombinant group V and X sPLA2s, direct addition of these enzymes to 293A cells suppressed both number and size of adenovirus plaque formation. Group V and X sPLA2s retarded the entry of adenovirus into endosomes. Moreover, adenoviral infection was suppressed by LPC (lysophosphatidylcholine), a membrane-hydrolytic product of these sPLA2s. Thus hydrolysis of the plasma membrane by these sPLA2s may eventually lead to the protection of host cells from adenovirus entry. Given that group V and X sPLA2s are expressed in human airway epithelium and macrophages and that the expression of endogenous group V sPLA2 is upregulated by virus-related stimuli in these cells, our present results raise the possibility that group V and X sPLA2s may play a role in innate immunity against adenoviral infection in the respiratory tract.
23
Lee, In-Chul, and Jong-Sup Bae. "Inhibitory Effect of Pelargonidin on Secretory Group IIA Phospholipase A2." Natural Product Communications 13, no. 8 (August 2018): 1934578X1801300. http://dx.doi.org/10.1177/1934578x1801300811.
Full textAbstract:
The expression of secretory group IIA phospholipase A2 (sPLA2-IIA) has been shown to be elevated in various inflammatory diseases, and lipopolysaccharide (LPS) up-regulates the expression of sPLA2-IIA in human umbilical vein endothelial cells (HUVECs). Pelargonidin (PEL) is a well-known red pigment found in plants, and has been reported as having important biological activities that are potentially beneficial for human health. Here, PEL was examined for its effects on the expression and activity of sPLA2-IIA in HUVECs and mouse. Post treatment of cells or mouse with PEL inhibited LPS-induced expression and activity of sPLA2-IIA. Therefore, these results suggest that PEL inhibited LPS mediated expression of sPLA2-IIA.
24
Styles, LA, CG Schalkwijk, AJ Aarsman, EP Vichinsky, BH Lubin, and FA Kuypers. "Phospholipase A2 levels in acute chest syndrome of sickle cell disease." Blood 87, no. 6 (March 15, 1996): 2573–78. http://dx.doi.org/10.1182/blood.v87.6.2573.bloodjournal8762573.
Full textAbstract:
Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.
25
Kang, Bu-Gyeong, Seung-Yeon Kwon, Hyo-Ran Lee, Yeji Hwang, So-Yeon Youn, Chulhong Oh, Jin-Byung Park, and Sun-Shin Cha. "Structural and functional characterization of a thermostable secretory phospholipase A2 from Sciscionella marina and its application in liposome biotransformation." Acta Crystallographica Section D Structural Biology 79, no. 2 (February 1, 2023): 188–97. http://dx.doi.org/10.1107/s2059798323000384.
Full textAbstract:
Secretory phospholipase A2 (sPLA2), which hydrolyzes the sn-2 acyl bond of lecithin in a Ca2+-dependent manner, is an important enzyme in the oil and oleochemical industries. However, most sPLA2s are not stable under process conditions. Therefore, a thermostable sPLA2 was investigated in this study. A marine bacterial sPLA2 isolated from Sciscionella marina (Sm-sPLA2) was catalytically active even after 5 h of incubation at high temperatures of up to 50°C, which is outstanding compared with a representative bacterial sPLA2 (i.e. sPLA2 from Streptomyces violaceoruber; Sv-sPLA2). Consistent with this, the melting temperature of Sm-sPLA2 was measured to be 7.7°C higher than that of Sv-sPLA2. Furthermore, Sm-sPLA2 exhibited an improved biotransformation performance compared with Sv-sPLA2 in the hydrolysis of soy lecithin to lysolecithin and free fatty acids at 50°C. Structural and mutagenesis studies revealed that the Trp41-mediated anchoring of a Ca2+-binding loop into the rest of the protein body is directly linked to the thermal stability of Sm-sPLA2. This finding provides a novel structural insight into the thermostability of sPLA2 and could be applied to create mutant proteins with enhanced industrial potential.
26
Arbibe, L., D. Vial, I. Rosinski-Chupin, N. Havet, M. Huerre, B. B. Vargaftig, and L. Touqui. "Endotoxin induces expression of type II phospholipase A2 in macrophages during acute lung injury in guinea pigs: involvement of TNF-alpha in lipopolysaccharide-induced type II phospholipase A2 synthesis." Journal of Immunology 159, no. 1 (July 1, 1997): 391–400. http://dx.doi.org/10.4049/jimmunol.159.1.391.
Full textAbstract:
Abstract Elevated levels of secretory type II phospholipase A2 (sPLA2-II) have been associated with a poor clinical outcome in the acute respiratory distress syndrome. This study identifies the cell source(s) and the mechanisms of sPLA2-II synthesis in the guinea pig model of acute respiratory distress syndrome induced by intratracheal injection of LPS. Administration of LPS led to an increase in lung membrane-associated calcium-dependent sPLA2 activity, which was abrogated by LY311727, a selective inhibitor of sPLA2-II. No sPLA2 activity was detected in the vascular compartment of the lung. LPS administration induced a parallel accumulation of sPLA2-II mRNA in lung tissues. In situ hybridization showed that sPLA2-II transcripts were synthesized in interstitial and alveolar macrophages (AM). Incubation of AM with LPS enhanced the expression of sPLA2-II mRNA, leading to stimulation of sPLA2-II synthesis and secretion. This increase was prevented by the addition of anti-TNF-alpha and anti-p55 TNF receptor Abs. Furthermore, the addition to AM of cellfree bronchoalveolar fluid collected from LPS-treated guinea pigs increased sPLA2-II expression, which was abrogated by anti-TNF-alpha Ab. These findings demonstrate that 1) macrophages are in vivo the major cell source of sPLA2-II in LPS-induced acute lung injury; 2) in contrast to that in other cell systems, regulation of LPS-induced sPLA2-II synthesis in AM is TNF-alpha dependent; and 3) production of TNF-alpha in the air-lung interface is an important step for sPLA2-II synthesis in macrophages.
27
Zhao, Hongxia, and Paavo K. J. Kinnunen. "Modulation of the Activity of Secretory Phospholipase A2 by Antimicrobial Peptides." Antimicrobial Agents and Chemotherapy 47, no. 3 (March 2003): 965–71. http://dx.doi.org/10.1128/aac.47.3.965-971.2003.
Full textAbstract:
ABSTRACT The antimicrobial peptides magainin 2, indolicidin, and temporins B and L were found to modulate the hydrolytic activity of secretory phospholipase A2 (sPLA2) from bee venom and in human lacrimal fluid. More specifically, hydrolysis of phosphatidylcholine (PC) liposomes by bee venom sPLA2 at 10 μM Ca2+ was attenuated by these peptides while augmented product formation was observed in the presence of 5 mM Ca2+. The activity of sPLA2 towards anionic liposomes was significantly enhanced by the antimicrobial peptides at low [Ca2+] and was further enhanced in the presence of 5 mM Ca2+. Similarly, with 5 mM Ca2+ the hydrolysis of anionic liposomes was enhanced significantly by human lacrimal fluid sPLA2, while that of PC liposomes was attenuated. These results indicate that concerted action of antimicrobial peptides and sPLA2 could improve the efficiency of the innate response to infections. Interestingly, inclusion of a cationic gemini surfactant in the vesicles showed an essentially similar pattern on sPLA2 activity, suggesting that the modulation of the enzyme activity by the antimicrobial peptides may involve also charge properties of the substrate surface.
28
Rodrigues, Caroline Fabri Bittencourt, Marcelo José Pena Ferreira, Mariana Novo Belchor, Caroline R. C. Costa, Danielle P. Novaes, Adeilso Bispo dos Santos Junior, Cinthia I. Tamayose, Marcus Vinícius Terashima Pinho, Marcos Antonio de Oliveira, and Marcos Hikari Toyama. "Evaluation of the Inhibitory Potential of Casuarictin, an Ellagitannin Isolated from White Mangrove (Laguncularia racemosa) Leaves, on Snake Venom Secretory Phospholipase A2." Marine Drugs 17, no. 7 (July 8, 2019): 403. http://dx.doi.org/10.3390/md17070403.
Full textAbstract:
Ellagitannins constitute the largest group of hydrolyzable tannins of plants, and, from this group, casuarictin (Casu) was identified in some plant species. However, to our knowledge, no investigation of secretory phospholipase A2 (sPLA2) inhibition by Casu has been performed yet. Casuarictin was isolated by chromatography n-butanol (n-BuOH) partition of Laguncularia racemosa leaves. The pharmacological and biological effects of Casu were evaluated on isolated sPLA2 from the rattlesnake (Crotalus durissus terrificus) and using a plant bacterial strain. The compound was able to form a protein complex consisting of a stable sPLA2 + Casu complex. Analyses carried out with matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF) revealed that the molecular mass of sPLA2 increased from 14,425.62 to 15,362.74 Da. The enzymatic activity of the sPLA2 + Casu complex was significantly lower than that of native sPLA2. Besides, molecular interactions of Casu with sPLA2 were able to virtually abolish the native edematogenic effect as well as myonecrosis induced by the protein when injected 10 min after sPLA2. Therefore, Casu may be considered a potential anti-inflammatory that can be used to treat edema and myonecrosis induced by serine-secreting phospholipase A2. In addition, the compound also showed great antimicrobial potential.
29
Styles, Lori A., Anton J. Aarsman, Elliott P. Vichinsky, and Frans A. Kuypers. "Secretory phospholipase A2 predicts impending acute chest syndrome in sickle cell disease." Blood 96, no. 9 (November 1, 2000): 3276–78. http://dx.doi.org/10.1182/blood.v96.9.3276.
Full textAbstract:
Abstract Acute chest syndrome (ACS) is the leading cause of death in sickle cell disease. Severe ACS often develops in the course of a vaso-occlusive crisis (VOC), but currently there are no predictors for its development. Secretory phospholipase A2(sPLA2), a potent inflammatory mediator, is elevated in ACS, and previous work suggests that sPLA2 predicts impending ACS. We prospectively evaluated sPLA2concentration during 21 admissions for VOC; 6 of these patients went on to develop ACS. Elevation of sPLA2 was detected all 6 patients 24 to 48 hours before ACS was clinically diagnosed. Adding the requirement for fever raised the specificity of sPLA2 to 87% while retaining 100% sensitivity. These data indicate that sPLA2 can be useful in alerting the clinician to patients with impending ACS. In addition, sPLA2 may be useful for instituting early therapies to prevent or reduce the clinical morbidity of ACS.
30
Styles, Lori A., Anton J. Aarsman, Elliott P. Vichinsky, and Frans A. Kuypers. "Secretory phospholipase A2 predicts impending acute chest syndrome in sickle cell disease." Blood 96, no. 9 (November 1, 2000): 3276–78. http://dx.doi.org/10.1182/blood.v96.9.3276.h8003276_3276_3278.
Full textAbstract:
Acute chest syndrome (ACS) is the leading cause of death in sickle cell disease. Severe ACS often develops in the course of a vaso-occlusive crisis (VOC), but currently there are no predictors for its development. Secretory phospholipase A2(sPLA2), a potent inflammatory mediator, is elevated in ACS, and previous work suggests that sPLA2 predicts impending ACS. We prospectively evaluated sPLA2concentration during 21 admissions for VOC; 6 of these patients went on to develop ACS. Elevation of sPLA2 was detected all 6 patients 24 to 48 hours before ACS was clinically diagnosed. Adding the requirement for fever raised the specificity of sPLA2 to 87% while retaining 100% sensitivity. These data indicate that sPLA2 can be useful in alerting the clinician to patients with impending ACS. In addition, sPLA2 may be useful for instituting early therapies to prevent or reduce the clinical morbidity of ACS.
31
Choi, Hyukjae, Sae-Kwang Ku, and Jong-Sup Bae. "Inhibitory Effect of Three Diketopiperazines from Marine-derived Bacteria on Secretory Group IIA Phospholipase A2." Natural Product Communications 11, no. 9 (September 2016): 1934578X1601100. http://dx.doi.org/10.1177/1934578x1601100919.
Full textAbstract:
Diketopiperazines, natural products found in bacteria, fungi, marine sponges, gorgonian and red algae, are cyclic dipeptides possessing relatively simple and rigid structures with chiral nature and various side chains. The compounds in this structure class have been known to possess diverse bioactivities including antibiotic activity, anti-cancer activity, neuroprotective activity, and anti-inflammatory activity. The expression of secretory group IIA phospholipase A2 (sPLA2-IIA) is enhanced by development of inflammatory disorders. Aim of this study is to determine the effects of diketopiperazines on the secretion and activity of sPLA2-IIA by lipopolysaccharide (LPS) in human umbilical vein endothelial cells (HUVECs). To do this, sPLA2-IIA expression was induced in the LPS-stimulated HUVECs and mice to evaluate the effect of diketopiperazines. Results showed that diketopiperazines remarkably suppressed the LPS-mediated protein expression and activity of sPLA2-IIA via inhibition of phosphorylation of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK) 1/2. These results demonstrated that diketopiperazines might play an important role in the modulation of sPLA2-IIA expression and activity in response to the inflammatory diseases.
32
KOUMANOV, Kamen, Claude WOLF, and Gilbert BÉREZIAT. "Modulation of human type II secretory phospholipase A2 by sphingomyelin and annexin VI." Biochemical Journal 326, no. 1 (August 15, 1997): 227–33. http://dx.doi.org/10.1042/bj3260227.
Full textAbstract:
Conjectural results have been reported on the capacity of inflammatory secreted phospholipase A2 (sPLA2) to hydrolyse mammalian membrane phospholipids. Development of an assay based on the release of non-esterified fatty acids by the enzyme acting on the organized phospholipid mixture constituting the membrane matrix has led to the identification of two prominent effectors, sphingomyelin (SPH) and annexin. Recombinant human type II sPLA2 hydrolyses red-cell membrane phospholipids with a marked preference for the inner leaflet. This preference is apparently related to the high content of SPH in the outer leaflet, which inhibits sPLA2. This inhibition by SPH is specific for sPLA2. Cholesterol counteracts the inhibition of sPLA2 by SPH, suggesting that the SPH-to-cholesterol ratio accounts in vivo for the variable susceptibility of cell membranes to sPLA2. Different effects were observed of the presence of the non-hydrolysable D-α-dipalmitoyl phosphatidylcholine (D-DPPC), which renders the membranes rigid but does not inhibit sPLA2. Annexin VI was shown, along with other annexins, to inhibit sPLA2 activity by sequestering the phospholipid substrate. The present study has provided the first evidence that annexin VI, in concentrations that inhibit hydrolysis of purified phospholipid substrates, stimulated the hydrolysis of membrane phospholipids by sPLA2. The activation requires the presence of membrane proteins. The effect is specific for type II sPLA2 and is not reproducible with type I PLA2. The activation by annexin VI of sPLA2 acting on red cell membranes results in the preferential release of polyunsaturated fatty acids. It suggests that type II sPLA2, in conjunction with annexin VI, might be involved in the final step of endocytosis and/or exocytosis providing the free polyunsaturated fatty acids acting synergistically to cause membrane fusion.
33
Petrovič, Uroš, Jernej Šribar, Maja Matis, Gregor Anderluh, Jasna Peter-Katalinić, Igor Križaj, and Franc Gubenšek. "Ammodytoxin, a secretory phospholipase A2, inhibits G2 cell-cycle arrest in the yeast Saccharomyces cerevisiae." Biochemical Journal 391, no. 2 (October 10, 2005): 383–88. http://dx.doi.org/10.1042/bj20050417.
Full textAbstract:
Ammodytoxin (Atx), an sPLA2 (secretory phospholipase A2), binds to γ and ε isoforms of porcine 14-3-3 proteins in vitro. 14-3-3 proteins are evolutionarily conserved eukaryotic regulatory proteins involved in a variety of biological processes, including cell-cycle regulation. We have now shown that Atx binds to yeast 14-3-3 proteins with an affinity similar to that for the mammalian isoforms. Thus yeast Saccharomyces cerevisiae can be used as a model eukaryotic cell, which lacks endogenous phospholipases A2, to assess the in vivo relevance of this interaction. Atx was expressed in yeast cells and shown to be biologically active inside the cells. It inhibited G2 cell-cycle arrest in yeast, which is regulated by 14-3-3 proteins. Interference with the cell cycle indicates a possible mechanism by which sPLA2s are able to cause the opposing effects, proliferation and apoptosis, in mammalian cells.
34
MASUDA, Seiko, Makoto MURAKAMI, Michiko MITSUISHI, Kazuo KOMIYAMA, Yukio ISHIKAWA, Toshiharu ISHII, and Ichiro KUDO. "Expression of secretory phospholipase A2 enzymes in lungs of humans with pneumonia and their potential prostaglandin-synthetic function in human lung-derived cells." Biochemical Journal 387, no. 1 (March 22, 2005): 27–38. http://dx.doi.org/10.1042/bj20041307.
Full textAbstract:
Although a number of sPLA2 (secretory phospholipase A2) enzymes have been identified in mammals, the localization and functions of individual enzymes in human pathologic tissues still remain obscure. In the present study, we have examined the expression and function of sPLA2s in human lung-derived cells and in human lungs with pneumonia. Group IID, V and X sPLA2s were expressed in cultured human bronchial epithelial cells (BEAS-2B) and normal human pulmonary fibroblasts with distinct requirement for cytokines (interleukin-1β, tumour necrosis factor α and interferon-γ). Lentivirus- or adenovirus-mediated transfection of various sPLA2s into BEAS-2B or normal human pulmonary fibroblast cells revealed that group V and X sPLA2s increased arachidonate release and prostaglandin production in both cell types, whereas group IIA and IID sPLA2s failed to do so. Immunohistochemistry of human lungs with pneumonia demonstrated that group V and X sPLA2s were widely expressed in the airway epithelium, interstitium and alveolar macrophages, in which group IID sPLA2 was also positive, whereas group IIA sPLA2 was restricted to the pulmonary arterial smooth muscle layers and bronchial chondrocytes, and group IIE and IIF sPLA2s were minimally detected. These results suggest that group V and X sPLA2s affect lung pathogenesis by facilitating arachidonate metabolism or possibly through other functions.
35
O'Donoghue, Michelle L., Ziad Mallat, David A. Morrow, Joelle Benessiano, Sarah Sloan, Torbjørn Omland, Scott D. Solomon, Eugene Braunwald, Alain Tedgui, and Marc S. Sabatine. "Prognostic Utility of Secretory Phospholipase A2 in Patients with Stable Coronary Artery Disease." Clinical Chemistry 57, no. 9 (September 1, 2011): 1311–17. http://dx.doi.org/10.1373/clinchem.2011.166520.
Full textAbstract:
BACKGROUND Secretory phospholipase A2 (sPLA2) may contribute to atherogenesis. To date, few prospective studies have examined the utility of sPLA2 for risk stratification in coronary artery disease (CAD). METHODS We measured plasma sPLA2 activity at baseline in 3708 subjects in the PEACE randomized trial of trandolapril vs placebo in stable CAD. Median follow-up was 4.8 years. We used Cox regression to adjust for demographics, clinical risk factors, apolipoprotein B, apolipoprotein A1, and medications. RESULTS After multivariable adjustment, sPLA2 was associated with an increased risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio Q4:Q1 1.55, 95% CI 1.13–2.14) and cardiovascular death or heart failure (1.91, 1.20–3.03). In further multivariable assessment, increased activity levels of sPLA2 were associated with the risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio 1.47, 95% CI 1.06–2.04), independent of lipoprotein-associated phospholipase A2 mass and C-reactive protein, and modestly improved the area under the curve (AUC) beyond established clinical risk factors (AUC 0.668–0.675, P = 0.01). sPLA2, N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T all were independently associated with cardiovascular death or heart failure, and each improved risk discrimination (P = 0.02, P < 0.001, P < 0.001, respectively). CONCLUSIONS sPLA2 activity provides independent prognostic information beyond established risk markers in patients with stable CAD. These data are encouraging for studies designed to evaluate the role of sPLA2 as a therapeutic target.
36
Ball, James B., Samina Y. Khan, Nathan JD McLaughlin, Rachelle Nuss, Laura Cole, and Christopher C. Silliman. "Hydroxyurea Treatment of Children with Sickle Cell Disease Inhibits RBC Membrane Degradation by Secretory Phospholipase a2." Blood 112, no. 11 (November 16, 2008): 1427. http://dx.doi.org/10.1182/blood.v112.11.1427.1427.
Full textAbstract:
Abstract Background: Secretory phospholipase A2 is an enzyme that is elevated in SCD patients with acute chest syndrome (ACS) and vaso-occlusive pain crisis (VOC) and inhibition of its enzymatic activity is in trials for ACS prevention (Styles LA. Blood.1996; 87:2573). This enzyme cleaves arachidonic acid from the phospholipids of red blood cell (RBC) membranes; and arachidonic acid can be converted to other pro-inflammatory lipid compounds (Murakami M. J Biochem.2002; 131:285). sPLA2 cleaves phosphatidylserine (PS) expressing lipid membranes. PS is usually in the inner leaflet (unexposed) in normal red blood cells (RBCs) but becomes externalized in sickle RBCs especially during VOC or ACS. There is modest exposure of PS during in the steady state among certain RBC populations (de Jong K. Br J Haematol.2006; 133:427). PS exposure allows sPLA2 to cleave RBC membranes, producing lipids which prime neutrophils (PMNs) and cause PMN-mediated pulmonary endothelial cell injury as the second event in a two-event model (Ball JB, Blood submitted). Objective: We hypothesize that sickle RBCs treated with hydroxyurea (HU) will be more resistant to digestion by sPLA2, thereby inhibiting the release of bioactive lipids. Design/Methods: Whole blood was collected from children with SCD when healthy or daily during admissions for VOC or ACS. The plasma and RBCs were separated. Plasma and lipids extracted from the plasma were used as priming agents of quiescent PMNs isolated from healthy donors. Additionally, the separated RBCs were treated with exogenous sPLA2, creating sPLA2-liberated lipids, which were also used as priming agents. The plasma sPLA2 levels were measured. Results: There was no difference in the sPLA2 levels of untreated and HU-treated SCD patients in the healthy condition (non-treated SCD: 12.8±3.1 ng/ml, HU: 12.2±4.2 ng/ml, p=0.95) and in VOC (non-treated SCD: 89.2 ± 79.3 ng/ml, HU: 86.5 ± 44.3 ng/ml, p=0.85). The PMN priming of the sPLA2-liberated lipids of untreated SCD patients, both healthy (*, Table 1) and those with VOC (#, Table 1), was elevated compared to the sPLA2-liberated lipids from HU-treated patients. We conclude that hydroxyurea treatment in vivo induces resistance to sPLA2 cleavage of RBC membrane lipids thereby inhibiting priming of PMNs, which has been implicated in PMN-mediated endothelial cell injury (Ball JB, Blood submitted). Table 1: PMN priming activity of plasma lipids and sPLA 2 -liberated lipids from patients with SCD. Healthy VOC pain plasma lipids sPLA2-liberated lipids plasma lipids sPLA2-liberated lipids * - p<0.01 compared to untreated plasma lipids from healthy untreated SCD patients # - p<0.01 compared to untreated plasma lipids from untreated SCD patients with VOC Hgb AA 2.55 ± 0.62 nmol O2-/min 1.94 ± 0.20 nmol O2-/min untreated SCD 2.21 ± 0.17 nmol O2-/min 3.19 ± 0.25 * nmol O2-/min 2.73 ± 0.24 nmol O2-/min 3.99 ± 0.28 # nmol O2-/min HU-treated SCD 2.34 ± 0.47 nmol O2-/min 2.75 ± 0.49 nmol O2-/min 2.23 ± 0.4 nmol O2-/min 2.69 ± 0.52 nmol O2-/min
37
Hite, R. Duncan, Bonnie L. Grier, B. Moseley Waite, Ruud A. Veldhuizen, Fred Possmayer, Li-Juan Yao, and Michael C. Seeds. "Surfactant protein B inhibits secretory phospholipase A2 hydrolysis of surfactant phospholipids." American Journal of Physiology-Lung Cellular and Molecular Physiology 302, no. 2 (January 15, 2012): L257—L265. http://dx.doi.org/10.1152/ajplung.00054.2011.
Full textAbstract:
Hydrolysis of surfactant phospholipids (PL) by secretory phospholipases A2 (sPLA2) contributes to surfactant damage in inflammatory airway diseases such as acute lung injury/acute respiratory distress syndrome. We and others have reported that each sPLA2 exhibits specificity in hydrolyzing different PLs in pulmonary surfactant and that the presence of hydrophilic surfactant protein A (SP-A) alters sPLA2-mediated hydrolysis. This report tests the hypothesis that hydrophobic SP-B also inhibits sPLA2-mediated surfactant hydrolysis. Three surfactant preparations were used containing varied amounts of SP-B and radiolabeled tracers of phosphatidylcholine (PC) or phosphatidylglycerol (PG): 1) washed ovine surfactant (OS) (pre- and postorganic extraction) compared with Survanta (protein poor), 2) Survanta supplemented with purified bovine SP-B (1–5%, wt/wt), and 3) a mixture of dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC), and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) (DPPC:POPC:POPG, 40:40:20) prepared as vesicles and monomolecular films in the presence or absence of SP-B. Hydrolysis of PG and PC by Group IB sPLA2 (PLA2G1A) was significantly lower in the extracted OS, which contains SP-B, compared with Survanta ( P = 0.005), which is SP-B poor. Hydrolysis of PG and PC in nonextracted OS, which contains all SPs, was lower than both Survanta and extracted OS. When Survanta was supplemented with 1% SP-B, PG and PC hydrolysis by PLA2G1B was significantly lower ( P < 0.001) than in Survanta alone. When supplemented into pure lipid vesicles and monomolecular films composed of PG and PC mixtures, SP-B also inhibited hydrolysis by both PLA2G1B and Group IIA sPLA2 (PLA2G2A). In films, PLA2G1B hydrolyzed surfactant PL monolayers at surface pressures ≤30 mN/m ( P < 0.01), and SP-B lowered the surface pressure range at which hydrolysis can occur. These results suggest the hydrophobic SP, SP-B, protects alveolar surfactant PL from hydrolysis mediated by multiple sPLA2 in both vesicles (alveolar subphase) and monomolecular films (air-liquid interface).
38
Pruzanski, W., F. C. de Beer, M. C. de Beer, E. Stefanski, and P. Vadas. "Serum amyloid A protein enhances the activity of secretory non-pancreatic phospholipase A2." Biochemical Journal 309, no. 2 (July 15, 1995): 461–64. http://dx.doi.org/10.1042/bj3090461.
Full textAbstract:
The acute-phase proteins serum amyloid A protein (SAA) and secretory phospholipase A2 (sPLA2) are simultaneously expressed during inflammatory conditions. SAA associates with high-density lipoprotein (HDL) altering its physicochemical composition. We found that purified acute-phase SAA, but not the constitutive form, markedly enhances the lipolytic activity of sPLA2 in a dose-related manner with phosphatidylcholine/lysophosphatidylcholine or phosphatidylethanolamine/lysophosphatidylethanolamine liposomal substrates. Normal HDL was found to reduce activity of sPLA2 in a dose-dependent manner, but when acute-phase HDL containing 27% SAA was tested, it enhanced sPLA2 activity. Immunopurified monospecific antibodies against SAA completely abolished the enhancing activity of SAA and acute-phase HDL. Given the central role of HDL in lipoprotein metabolism, the interaction between HDL, SAA and sPLA2 may account for changes detected in lipoprotein metabolism during the acute phase.
39
Nakashima, Akina, Susumu Tomono, Tatsuya Yamazaki, Masanori Inui, Naoko Morita, Isao Ichimonji, Hidekazu Takagi, et al. "Phospholipase A2 from bee venom increases poly(I:C)-induced activation in human keratinocytes." International Immunology 32, no. 6 (January 20, 2020): 371–83. http://dx.doi.org/10.1093/intimm/dxaa005.
Full textAbstract:
Abstract Bee venom (BV) induces skin inflammation, characterized by erythema, blisters, edemas, pain and itching. Although BV has been found to have an inhibitory effect on toll-like receptors (TLRs), we here show that BV enhances keratinocyte responses to polyinosinic-polycytidylic acid [poly(I:C)], a ligand for TLR3. Our results revealed that the enhanced TLR activity was primarily induced by secretory phospholipase A2 (sPLA2), a component of BV (BV-sPLA2). PLA2 mediates the hydrolysis of membrane phospholipids into lysophospholipids and free fatty acids. We demonstrated that BV-sPLA2 increased the intracellular uptake of poly(I:C), phosphorylation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), and poly(I:C)-mediated interleukin 8 production in human keratinocytes. We further showed that the enzymatic activity of BV-sPLA2 was essential for the increased uptake of poly(I:C). These findings suggest that BV-sPLA2 may induce a modification of the cell membrane structure, leading to enhanced poly(I:C) uptake in keratinocytes. BV-sPLA2 might be able to promote wound healing by enhancing TLR3 responses.
40
Autilio, Chiara, Shivani Shankar-Aguilera, Angelo Minucci, Lhoussaine Touqui, and Daniele De Luca. "Effect of cooling on lung secretory phospholipase A2 activity in vitro, ex vivo, and in vivo." American Journal of Physiology-Lung Cellular and Molecular Physiology 316, no. 3 (March 1, 2019): L498—L505. http://dx.doi.org/10.1152/ajplung.00201.2018.
Full textAbstract:
Hypothermia can modify surfactant composition and function. Secretory phospholipase A2 (sPLA2) hydrolyses surfactant phospholipids and is important in the pathobiology of several critical respiratory disorders. We hypothesize that sPLA2 activity might be influenced by the temperature partially explaining surfactant changes. This study aims to evaluate comprehensively the effect of hypothermia on sPLA2 activity. We measured sPLA2 activity at different temperatures, alone or combined with bile acids, in vitro (incubating human recombinant sPLA2-IIA and porcine sPLA2-IB), ex vivo (by cooling bronchoalveolar lavage samples from neonates with respiratory distress syndrome or no lung disease), and in vivo (using lavage samples obtained before and after 72 h of whole body cooling in neonates with hypoxic-ischemic encephalopathy). We also measured concentrations of various sPLA2 subtypes and natural sPLA2 inhibitors in in vivo cooled samples. Results were corrected for protein content and dilution. In vitro cooling did not show any effect of hypothermia on sPLA2. Ex vivo cooling did not alter total sPLA2 activity, and the addition of bile acids increased sPLA2 activity irrespective of the temperature and the type of sampled patient. In vivo hypothermia reduced median sPLA2 activity from 16.6 [15.2–106.7] IU/mg to 3.3 [2.7–8.5] IU/mg ( P = 0.026) and mean sPLA2-IIA from 1.1 (0.8) pg/μg to 0.6 (0.4) pg/μg ( P = 0.047), whereas dioleylphosphatidylglycerol increased from 8.3 (3.9)% to 12.8 (5.1)% ( P = 0.02). Whole body hypothermia decreases in vivo global sPLA2 activity in bronchoalveolar lavage fluids through the reduction of sPLA2-IIA and increment of dioleylphosphatidylglycerol. This effect is absent during in vitro or ex vivo hypothermia.
41
Watanabe, Kazuhiro, Yoshitaka Taketomi, Yoshimi Miki, Kiyotaka Kugiyama, and Makoto Murakami. "Group V secreted phospholipase A2 plays a protective role against aortic dissection." Journal of Biological Chemistry 295, no. 30 (June 1, 2020): 10092–111. http://dx.doi.org/10.1074/jbc.ra120.013753.
Full textAbstract:
Aortic dissection is a life-threatening aortopathy involving separation of the aortic wall, whose underlying mechanisms are still incompletely understood. Epidemiological evidence suggests that unsaturated fatty acids improve cardiovascular health. Here, using quantitative RT-PCR, histological analyses, magnetic cell sorting and flow cytometry assays, and MS-based lipidomics, we show that the activity of a lipid-metabolizing enzyme, secreted phospholipase A2 group V (sPLA2-V), protects against aortic dissection by endogenously mobilizing vasoprotective lipids. Global and endothelial cell–specific sPLA2-V–deficient mice frequently developed aortic dissection shortly after infusion of angiotensin II (AT-II). We observed that in the AT-II–treated aorta, endothelial sPLA2-V mobilized oleic and linoleic acids, which attenuated endoplasmic reticulum stress, increased the expression of lysyl oxidase, and thereby stabilized the extracellular matrix in the aorta. Of note, dietary supplementation with oleic or linoleic acid reversed the increased susceptibility of sPLA2-V–deficient mice to aortic dissection. These findings reveal an unexplored functional link between sPLA2-driven phospholipid metabolism and aortic stability, possibly contributing to the development of improved diagnostic and/or therapeutic strategies for preventing aortic dissection.
42
Giresha, Aladahalli S., Deepadarshan Urs, Sophiya Pundalik, Rajkumar S. Meti, Siddanakoppalu N. Pramod, Ballenahalli H. Supreetha, Madhusudana Somegowda, et al. "Sinapicacid Inhibits Group IIA Secretory Phospholipase A2 and Its Inflammatory Response in Mice." Antioxidants 11, no. 7 (June 25, 2022): 1251. http://dx.doi.org/10.3390/antiox11071251.
Full textAbstract:
Human Group IIA secreted phospholipase A2 (sPLA2-IIA) enzyme plays a crucial role in several chronic inflammatory diseases such asasthma, atherosclerosis, gout, bronchitis, etc. Several studies showed that the antioxidants exert an anti-inflammatory function by inhibiting the sPLA2-IIA enzyme. Hence, the present study evaluated an antioxidant molecule, sinapic acid, for sPLA2-IIA inhibition as an anti-inflammatory function. Initially, the antioxidant efficacy of sinapic acid was evaluated, and it showed greater antioxidant potency. Further, sinapic acid inhibited 94.4 ± 4.83% of sPLA2-IIA activity with an IC50 value of 4.16 ± 0.13 µM. The mode of sPLA2-IIA inhibition was examined by increasing the substrate concentration from 30 to 120nM and the calcium concentration from 2.5 to 15 mM, which did not change the level of inhibition. Further, sinapic acid altered the intrinsic fluorescence and distorted the far UltraViolet Circular Dichroism (UV-CD) spectra of the sPLA2-IIA, indicating the direct enzyme-inhibitor interaction. Sinapic acid reduced the sPLA2-IIA mediated hemolytic activity from 94 ± 2.19% to 12.35 ± 2.57% and mouse paw edema from 171.75 ± 2.2% to 114.8 ± 1.98%, demonstrating the anti-inflammatory efficiency of sinapic acid by in situ and in vivo methods, respectively. Finally, sinapic acid reduced the hemorrhagic effect of Vipera russelli venom hemorrhagic complex-I (VR-HC-I) as an anti-hemorrhagic function. Thus, the above experimental results revealed the sinapic acid potency to be an antioxidant, anti-inflammatory and anti-hemorrhagic molecule, and therefore, it appears to be a promising therapeutic agent.
43
SUN, Yong-Xin, Kazuhito TSUBOI, Yasuo OKAMOTO, Takeharu TONAI, Makoto MURAKAMI, Ichiro KUDO, and Natsuo UEDA. "Biosynthesis of anandamide and N-palmitoylethanolamine by sequential actions of phospholipase A2 and lysophospholipase D." Biochemical Journal 380, no. 3 (June 15, 2004): 749–56. http://dx.doi.org/10.1042/bj20040031.
Full textAbstract:
Anandamide (an endocannabinoid) and other bioactive long-chain NAEs (N-acylethanolamines) are formed by direct release from N-acyl-PE (N-acyl-phosphatidylethanolamine) by a PLD (phospholipase D). However, the possible presence of a two-step pathway from N-acyl-PE has also been suggested previously, which comprises (1) the hydrolysis of N-acyl-PE to N-acyl-lysoPE by PLA1/PLA2 enzyme(s) and (2) the release of NAEs from N-acyllysoPE by lysoPLD (lysophospholipase D) enzyme(s). In the present study we report for the first time the characterization of enzymes responsible for this pathway. The PLA1/PLA2 activity for N-palmitoyl-PE was found in various rat tissues, with the highest activity in the stomach. This stomach enzyme was identified as group IB sPLA2 (secretory PLA2), and its product was determined as N-acyl-1-acyl-lysoPE. Recombinant group IB, IIA and V of sPLA2s were also active with N-palmitoyl-PE, whereas group X sPLA2 and cytosolic PLA2α were inactive. In addition, we found wide distribution of lysoPLD activity generating N-palmitoylethanolamine from N-palmitoyl-lysoPE in rat tissues, with higher activities in the brain and testis. Based on several lines of enzymological evidence, the lysoPLD enzyme could be distinct from the known N-acyl-PE-hydrolysing PLD. sPLA2-IB dose dependently enhanced the production of N-palmitoylethanolamine from N-palmitoyl-PE in the brain homogenate showing the lysoPLD activity. N-Arachidonoyl-PE and N-arachidonoyl-lysoPE as anandamide precursors were also good substrates of sPLA2-IB and the lysoPLD respectively. These results suggest that the sequential actions of PLA2 and lysoPLD may constitute another biosynthetic pathway for NAEs, including anandamide.
44
Leiguez, Elbio, Priscila Motta, Rodrigo Maia Marques, Bruno Lomonte, Suely Vilela Sampaio, and Catarina Teixeira. "A Representative GIIA Phospholipase A2 Activates Preadipocytes to Produce Inflammatory Mediators Implicated in Obesity Development." Biomolecules 10, no. 12 (November 24, 2020): 1593. http://dx.doi.org/10.3390/biom10121593.
Full textAbstract:
Adipose tissue secretes proinflammatory mediators which promote systemic and adipose tissue inflammation seen in obesity. Group IIA (GIIA)-secreted phospholipase A2 (sPLA2) enzymes are found to be elevated in plasma and adipose tissue from obese patients and are active during inflammation, generating proinflammatory mediators, including prostaglandin E2 (PGE2). PGE2 exerts anti-lipolytic actions and increases triacylglycerol levels in adipose tissue. However, the inflammatory actions of GIIA sPLA2s in adipose tissue cells and mechanisms leading to increased PGE2 levels in these cells are unclear. This study investigates the ability of a representative GIIA sPLA2, MT-III, to activate proinflammatory responses in preadipocytes, focusing on the biosynthesis of prostaglandins, adipocytokines and mechanisms involved in these effects. Our results showed that MT-III induced biosynthesis of PGE2, PGI2, MCP-1, IL-6 and gene expression of leptin and adiponectin in preadipocytes. The MT-III-induced PGE2 biosynthesis was dependent on cytosolic PLA2 (cPLA2)-α, cyclooxygenases (COX)-1 and COX-2 pathways and regulated by a positive loop via the EP4 receptor. Moreover, MT-III upregulated COX-2 and microsomal prostaglandin synthase (mPGES)-1 protein expression. MCP-1 biosynthesis induced by MT-III was dependent on the EP4 receptor, while IL-6 biosynthesis was dependent on EP3 receptor engagement by PGE2. These data highlight preadipocytes as targets for GIIA sPLA2s and provide insight into the roles played by this group of sPLA2s in obesity.
45
Rys-Sikora, Krystyna E., Raymond L. Konger, John W. Schoggins, Rama Malaviya, and Alice P. Pentland. "Coordinate expression of secretory phospholipase A2 and cyclooxygenase-2 in activated human keratinocytes." American Journal of Physiology-Cell Physiology 278, no. 4 (April 1, 2000): C822—C833. http://dx.doi.org/10.1152/ajpcell.2000.278.4.c822.
Full textAbstract:
PGE2 levels are altered in human epidermis after in vivo wounding; however, mechanisms modulating PGE2 production in activated keratinocytes are unclear. In previous studies, we showed that PGE2 is a growth-promoting autacoid in human primary keratinocyte cultures, and its production is modulated by plating density, suggesting that regulated PGE2 synthesis is an important component of wound healing. Here, we examine the role of phospholipase A2(PLA2) and cyclooxygenase (COX) enzymes in modulation of PGE2 production. We report that the increased PGE2 production that occurs in keratinocytes grown in nonconfluent conditions is also observed after in vitro wounding, indicating that similar mechanisms are involved. This increase was associated with coordinate upregulation of both COX-2 and secretory PLA2 (sPLA2) proteins. Increased sPLA2 activity was also observed. By RT-PCR, we identified the presence of type IIA and type V sPLA2, along with the M-type sPLA2 receptor. Thus the coordinate expression of sPLA2 and COX-2 may be responsible for the increased prostaglandin synthesis in activated keratinocytes during wound repair.
46
Lewin, Matthew, José Gutiérrez, Stephen Samuel, María Herrera, Wendy Bryan-Quirós, Bruno Lomonte, Philip Bickler, Tommaso Bulfone, and David Williams. "Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom." Toxins 10, no. 10 (September 20, 2018): 380. http://dx.doi.org/10.3390/toxins10100380.
Full textAbstract:
There is an unmet need for economical snakebite therapies with long shelf lives that are effective even with delays in treatment. The orally bioavailable, heat-stable, secretory phospholipase A2 (sPLA2) inhibitor, LY333013, demonstrates antidotal characteristics for severe snakebite envenoming in both field and hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus scutellatus) demonstrates that LY333013, even with delayed oral administration, improves the chances of survival. Furthermore, LY333013 improves the performance of antivenom even after it no longer reverses neurotoxic signs. Our study is the first demonstration that neurotoxicity from presynaptic venom sPLA2S can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA2 inhibitors have the potential to reduce death and disability and should be considered for the initial and adjunct treatment of snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to achieve these endpoints requires further investigation and development efforts.
47
Nijmeijer, R., M. Willemsen, C. J. L. M. Meijer, C. A. Visser, R. H. Verheijen, R. A. Gottlieb, C. E. Hack, and H. W. M. Niessen. "Type II secretory phospholipase A2 binds to ischemic flip-flopped cardiomyocytes and subsequently induces cell death." American Journal of Physiology-Heart and Circulatory Physiology 285, no. 5 (November 2003): H2218—H2224. http://dx.doi.org/10.1152/ajpheart.00887.2002.
Full textAbstract:
Type II secretory phospholipase A2 (sPLA2) is a cardiovascular risk factor. We recently found depositions of sPLA2 in the necrotic center of infarcted human myocardium and normally appearing cardiomyocytes adjacent to the border zone. The consequences of binding of sPLA2 to ischemic cardiomyocytes are not known. To explore a potential effect of sPLA2 on ischemic cardiomyocytes at a cellular level we used an in vitro model. The cardiomyocyte cell line H9c2 or adult cardiomyocytes were isolated from rabbits that were incubated with sPLA2 in the presence of metabolic inhibitors to mimic ischemia-reperfusion conditions. Cell viability was established with the use of annexin V and propidium iodide or 7-aminoactinomycin D. Metabolic inhibition induced an increase of the number of flip-flopped cells, including a population that did not stain with propidium iodide and that was caspase-3 negative. sPLA2 bound to the flip-flopped cells, including those negative for caspase-3. sPLA2 binding induced cell death in these latter cells. In addition, sPLA2 potentiated the binding of C-reactive protein (CRP) to these cells. We conclude that by binding to flip-flopped cardiomyocytes, including those that are caspase-3 negative and presumably reversibly injured, sPLA2 may induce cell death and tag these cells with CRP.
48
DONG, Chang-Zhi, Anthony ROMIEU, Carine M. MOUNIER, Françoise HEYMANS, Bernard P. ROQUES, and Jean-Jacques GODFROID. "Total direct chemical synthesis and biological activities of human group IIA secretory phospholipase A2." Biochemical Journal 365, no. 2 (July 15, 2002): 505–11. http://dx.doi.org/10.1042/bj20011648.
Full textAbstract:
Human group IIA secretory phospholipase A2 (hGIIA sPLA2) is reported to be involved in inflammation, since its expression level is enhanced under various inflammatory conditions. In this work, we report the total chemical synthesis of this enzyme (124 amino acids) by solid-phase method. The identity of the protein, in denatured or folded (7 disulphide bonds) forms, was confirmed by electrospray MS. Synthetic sPLA2 possesses the same circular dichroism spectrum, enzymic activity in hydrolysing different phospholipid substrates, and inhibitory effect in thrombin formation from prothrombinase complex as the recombinant sPLA2. Furthermore, LY311727, a reported specific hGIIA sPLA2 inhibitor, is able to inhibit the synthetic and the recombinant enzymes with the same efficiency. This study demonstrates that chemically continuous solid phase synthesis is an alternative and less time-consuming approach to producing small, structurally folded and fully active proteins of up to 124 amino acids, such as hGIIA sPLA2. Moreover, this technique provides more flexibility in analogue synthesis to elucidate their physiological functions and pathological effects.
49
Ewing, Heather, Virneliz Fernández-Vega, Timothy P. Spicer, Peter Chase, Steven Brown, Louis Scampavia, William R. Roush, et al. "Fluorometric High-Throughput Screening Assay for Secreted Phospholipases A2 Using Phospholipid Vesicles." Journal of Biomolecular Screening 21, no. 7 (July 10, 2016): 713–21. http://dx.doi.org/10.1177/1087057116646742.
Full textAbstract:
There is interest in developing inhibitors of human group III secreted phospholipase A2 (hGIII-sPLA2) because this enzyme plays a role in mast cell maturation. There are no potent inhibitors for hGIII-sPLA2 reported to date, so we adapted a fluorescence-based enzyme activity monitoring method to a high-throughput screening format. We opted to use an assay based on phospholipid substrate present in phospholipid vesicles since this matrix more closely resembles the natural substrate of hGIII-sPLA2, as opposed to phospholipid/detergent mixed micelles. The substrate is a phospholipid analogue containing BODIPY fluorophores dispersed as a minor component in vesicles of nonfluorescent phospholipids. Action of hGIII-sPLA2 liberates a free fatty acid from the phospholipid, leading to a reduction in quenching of the fluorophore and hence an increase in fluorescence. The assay uses optical detection in a 1536-well plate format with an excitation wavelength far away from the UV range so as to minimize false-positive library hits that result from quenching of the fluorescence. The high-throughput screen was successfully carried out on a library of 370,276 small molecules. Several hits were discovered, and data have been uploaded to PubChem. This study describes the first high-throughput optical screening assay for secreted phospholipase A2 inhibitors based on a phospholipid vesicle substrate.
50
Kirschnek, Susanne, and Erich Gulbins. "Phospholipase A2 Functions in Pseudomonas aeruginosa- Induced Apoptosis." Infection and Immunity 74, no. 2 (February 2006): 850–60. http://dx.doi.org/10.1128/iai.74.2.850-860.2006.
Full textAbstract:
ABSTRACT Pseudomonas aeruginosa, a gram-negative, facultative pathogen, causes severe and often even lethal infections in immunocompromised patients, as well as cystic fibrosis patients. We show here that a variety of P. aeruginosa strains activate phospholipase A2 (PLA2), cultured epithelial cells, and fibroblasts, resulting in increased intracellular and extracellular arachidonic acid release. The use of different PLA2 inhibitors revealed that P. aeruginosa-induced arachidonic acid release is mediated by activation of cytosolic PLA2 (cPLA2), whereas iPLA2 or sPLA2 do not seem to be involved in the response to P. aeruginosa. Likewise, the cPLA2-specific inhibitors MAFP and AACOCF3 prevented apoptosis of cultured epithelial cells upon P. aeruginosa infection, whereas inhibitors specific for iPLA2 or sPLA2 were without effect. The physiological significance of these findings is indicated by an inhibition of apoptosis in tracheal epithelial cells upon in vivo infection with P. aeruginosa. The data indicate that arachidonic acid generation by activation of cPLA2 during P. aeruginosa infection plays an important role in the induction of host cell death.