Journal articles: 'P-IV ATPase'

1

Halleck, Margaret S., Robert A. Schlegel, and Patrick L. Williamson. "Reanalysis of ATP11B, a Type IV P-type ATPase." Journal of Biological Chemistry 277, no. 12 (January 14, 2002): 9736–40. http://dx.doi.org/10.1074/jbc.m200240200.

Full text

APA, Harvard, Vancouver, ISO, and other styles

2

Roland, Bartholomew P., and Todd R. Graham. "Directed evolution of a sphingomyelin flippase reveals mechanism of substrate backbone discrimination by a P4-ATPase." Proceedings of the National Academy of Sciences 113, no. 31 (July 18, 2016): E4460—E4466. http://dx.doi.org/10.1073/pnas.1525730113.

Full text

Abstract:

Phospholipid flippases in the type IV P-type ATPase (P4-ATPases) family establish membrane asymmetry and play critical roles in vesicular transport, cell polarity, signal transduction, and neurologic development. All characterized P4-ATPases flip glycerophospholipids across the bilayer to the cytosolic leaflet of the membrane, but how these enzymes distinguish glycerophospholipids from sphingolipids is not known. We used a directed evolution approach to examine the molecular mechanisms through which P4-ATPases discriminate substrate backbone. A mutagenesis screen in the yeast Saccharomyces cerevisiae has identified several gain-of-function mutations in the P4-ATPase Dnf1 that facilitate the transport of a novel lipid substrate, sphingomyelin. We found that a highly conserved asparagine (N220) in the first transmembrane segment is a key enforcer of glycerophospholipid selection, and specific substitutions at this site allow transport of sphingomyelin.

APA, Harvard, Vancouver, ISO, and other styles

3

Theorin, Lisa, Kristina Faxén, Danny Mollerup Sørensen, Rebekka Migotti, Gunnar Dittmar, Jürgen Schiller, David L. Daleke, Michael Palmgren, Rosa Laura López-Marqués, and Thomas Günther Pomorski. "The lipid head group is the key element for substrate recognition by the P4 ATPase ALA2: a phosphatidylserine flippase." Biochemical Journal 476, no. 5 (March 6, 2019): 783–94. http://dx.doi.org/10.1042/bcj20180891.

Full text

Abstract:

Abstract Type IV P-type ATPases (P4 ATPases) are lipid flippases that catalyze phospholipid transport from the exoplasmic to the cytoplasmic leaflet of cellular membranes, but the mechanism by which they recognize and transport phospholipids through the lipid bilayer remains unknown. In the present study, we succeeded in purifying recombinant aminophospholipid ATPase 2 (ALA2), a member of the P4 ATPase subfamily in Arabidopsis thaliana, in complex with the ALA-interacting subunit 5 (ALIS5). The ATP hydrolytic activity of the ALA2–ALIS5 complex was stimulated in a highly specific manner by phosphatidylserine. Small changes in the stereochemistry or the functional groups of the phosphatidylserine head group affected enzymatic activity, whereas alteration in the length and composition of the acyl chains only had minor effects. Likewise, the enzymatic activity of the ALA2–ALIS5 complex was stimulated by both mono- and di-acyl phosphatidylserines. Taken together, the results identify the lipid head group as the key structural element for substrate recognition by the P4 ATPase.

APA, Harvard, Vancouver, ISO, and other styles

4

Costa, Sara R., Magdalena Marek, Kristian B. Axelsen, Lisa Theorin, Thomas G. Pomorski, and Rosa L. López-Marqués. "Role of post-translational modifications at the β-subunit ectodomain in complex association with a promiscuous plant P4-ATPase." Biochemical Journal 473, no. 11 (May 27, 2016): 1605–15. http://dx.doi.org/10.1042/bcj20160207.

Full text

Abstract:

P-type ATPases of subfamily IV (P4-ATPases) constitute a major group of phospholipid flippases that form heteromeric complexes with members of the Cdc50 (cell division control 50) protein family. Some P4-ATPases interact specifically with only one β-subunit isoform, whereas others are promiscuous and can interact with several isoforms. In the present study, we used a site-directed mutagenesis approach to assess the role of post-translational modifications at the plant ALIS5 β-subunit ectodomain in the functionality of the promiscuous plant P4-ATPase ALA2. We identified two N-glycosylated residues, Asn181 and Asn231. Whereas mutation of Asn231 seems to have a small effect on P4-ATPase complex formation, mutation of evolutionarily conserved Asn181 disrupts interaction between the two subunits. Of the four cysteine residues located in the ALIS5 ectodomain, mutation of Cys86 and Cys107 compromises complex association, but the mutant β-subunits still promote complex trafficking and activity to some extent. In contrast, disruption of a conserved disulfide bond between Cys158 and Cys172 has no effect on the P4-ATPase complex. Our results demonstrate that post-translational modifications in the β-subunit have different functional roles in different organisms, which may be related to the promiscuity of the P4-ATPase.

APA, Harvard, Vancouver, ISO, and other styles

5

Flamant, Stéphane, Pascale Pescher, Brigitte Lemercier, Mathieu Clément-Ziza, François Képès, Marc Fellous, Geneviève Milon, Gilles Marchal, and Claude Besmond. "Characterization of a putative type IV aminophospholipid transporter P-type ATPase." Mammalian Genome 14, no. 1 (January 1, 2003): 21–30. http://dx.doi.org/10.1007/s00335-002-3032-3.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Hiraizumi, Masahiro, Keitaro Yamashita, Tomohiro Nishizawa, and Osamu Nureki. "Cryo-EM structures capture the transport cycle of the P4-ATPase flippase." Science 365, no. 6458 (August 15, 2019): 1149–55. http://dx.doi.org/10.1126/science.aay3353.

Full text

Abstract:

In eukaryotic membranes, type IV P-type adenosine triphosphatases (P4-ATPases) mediate the translocation of phospholipids from the outer to the inner leaflet and maintain lipid asymmetry, which is critical for membrane trafficking and signaling pathways. Here, we report the cryo–electron microscopy structures of six distinct intermediates of the human ATP8A1-CDC50a heterocomplex at resolutions of 2.6 to 3.3 angstroms, elucidating the lipid translocation cycle of this P4-ATPase. ATP-dependent phosphorylation induces a large rotational movement of the actuator domain around the phosphorylation site in the phosphorylation domain, accompanied by lateral shifts of the first and second transmembrane helices, thereby allowing phosphatidylserine binding. The phospholipid head group passes through the hydrophilic cleft, while the acyl chain is exposed toward the lipid environment. These findings advance our understanding of the flippase mechanism and the disease-associated mutants of P4-ATPases.

APA, Harvard, Vancouver, ISO, and other styles

7

Xu, Zongchang, Prince Marowa, Han Liu, Haina Du, Chengsheng Zhang, and Yiqiang Li. "Genome-Wide Identification and Analysis of P-Type Plasma Membrane H+-ATPase Sub-Gene Family in Sunflower and the Role of HHA4 and HHA11 in the Development of Salt Stress Resistance." Genes 11, no. 4 (March 27, 2020): 361. http://dx.doi.org/10.3390/genes11040361.

Full text

Abstract:

The P-type plasma membrane (PM) H+-ATPase plays a major role during the growth and development of a plant. It is also involved in plant resistance to a variety of biotic and abiotic factors, including salt stress. The PM H+-ATPase gene family has been well characterized in Arabidopsis and other crop plants such as rice, cucumber, and potato; however, the same cannot be said in sunflower (Helianthus annuus). In this study, a total of thirteen PM H+-ATPase genes were screened from the recently released sunflower genome database with a comprehensive genome-wide analysis. According to a systematic phylogenetic classification with a previously reported species, the sunflower PM H+-ATPase genes (HHAs) were divided into four sub-clusters (I, II, IV, and V). In addition, systematic bioinformatics analyses such as gene structure analysis, chromosome location analysis, subcellular localization predication, conserved motifs, and Cis-acting elements of promoter identification were also done. Semi-quantitative PCR analysis data of HHAs in different sunflower tissues revealed the specificity of gene spatiotemporal expression and sub-cluster grouping. Those belonging to sub-cluster I and II exhibited wide expression in almost all of the tissues studied while sub-cluster IV and V seldom showed expression. In addition, the expression of HHA4, HHA11, and HHA13 was shown to be induced by salt stress. The transgenic plants overexpressing HHA4 and HHA11 showed higher salinity tolerance compared with wild-type plants. Further analysis showed that the Na+ content of transgenic Arabidopsis plants decreased under salt stress, which indicates that PM H+ ATPase participates in the physiological process of Na+ efflux, resulting in salt resistance of the plants. This study is the first to identify and analyze the sunflower PM H+ ATPase gene family. It does not only lay foundation for future research but also demonstrates the role played by HHAs in salt stress tolerance.

APA, Harvard, Vancouver, ISO, and other styles

8

Calderón-Guzmán, David, Norma Osnaya-Brizuela, Raquel García-Alvarez, Ernestina Hernández-García, and Hugo Juárez-Olguín. "Oxidative stress induced by morphine in brain of rats fed with a protein deficient diet." Human & Experimental Toxicology 28, no. 9 (September 2009): 577–82. http://dx.doi.org/10.1177/0960327109102798.

Full text

Abstract:

The objective of the study is to determine the damage by oxidative stress induced by morphine in brain of rats fed with a protein-deficient diet. Twenty-eight malnourished male Wistar rats, 30 days old, were used in the study. The animals were divided into four groups of 7 rats per group. Group I received NaCl and the groups II; III and IV intraperitoneally received 3, 6 and 12 mg/kg of morphine sulphate, respectively, in a single dose. Animals were sacrificed and the levels of glutathione (GSH), dopamine, tryptophan and 5-hydroxyindole-3-acetic acid (5-HIAA) as well as, Na+/K+ ATPase and total ATPase activity in the brain were measured. Tryptophan levels and Na+/K + ATPase activity showed non-significant changes in the experimental group. Levels of 5-HIAA decreased significantly (p = .03) in animals that received 12 mg/kg of morphine and in animals that received 3 mg/kg, levels of GSH and dopamine were found to have a significant decrease (p < .05), but a significant increase in the group that received 12 mg/kg of morphine (p < .05). Total ATPase activity increased significantly in the groups that received 3 mg/kg (p = .015) and 6 mg/kg (p = .0001) of morphine. The results show that malnutrition induces changes in cellular regulation and biochemical responses to oxidative stress caused by morphine sulphate.

APA, Harvard, Vancouver, ISO, and other styles

9

Jain, Bhawik Kumar, Bartholomew P. Roland, and Todd R. Graham. "Exofacial membrane composition and lipid metabolism regulates plasma membrane P4-ATPase substrate specificity." Journal of Biological Chemistry 295, no. 52 (October 15, 2020): 17997–8009. http://dx.doi.org/10.1074/jbc.ra120.014794.

Full text

Abstract:

The plasma membrane of a cell is characterized by an asymmetric distribution of lipid species across the exofacial and cytofacial aspects of the bilayer. Regulation of membrane asymmetry is a fundamental characteristic of membrane biology and is crucial for signal transduction, vesicle transport, and cell division. The type IV family of P-ATPases, or P4-ATPases, establishes membrane asymmetry by selection and transfer of a subset of membrane lipids from the lumenal or exofacial leaflet to the cytofacial aspect of the bilayer. It is unclear how P4-ATPases sort through the spectrum of membrane lipids to identify their desired substrate(s) and how the membrane environment modulates this activity. Therefore, we tested how the yeast plasma membrane P4-ATPase, Dnf2, responds to changes in membrane composition induced by perturbation of endogenous lipid biosynthetic pathways or exogenous application of lipid. The primary substrates of Dnf2 are glucosylceramide (GlcCer) and phosphatidylcholine (PC, or their lyso-lipid derivatives), and we find that these substrates compete with each other for transport. Acutely inhibiting sphingolipid synthesis using myriocin attenuates transport of exogenously applied GlcCer without perturbing PC transport. Deletion of genes controlling later steps of glycosphingolipid production also perturb GlcCer transport to a greater extent than PC transport. In contrast, perturbation of ergosterol biosynthesis reduces PC and GlcCer transport equivalently. Surprisingly, application of lipids that are poor transport substrates differentially affects PC and GlcCer transport by Dnf2, thus altering substrate preference. Our data indicate that Dnf2 exhibits exquisite sensitivity to the membrane composition, thus providing feedback onto the function of the P4-ATPases.

APA, Harvard, Vancouver, ISO, and other styles

10

Zhou, X., and T. R. Graham. "Reconstitution of phospholipid translocase activity with purified Drs2p, a type-IV P-type ATPase from budding yeast." Proceedings of the National Academy of Sciences 106, no. 39 (September 15, 2009): 16586–91. http://dx.doi.org/10.1073/pnas.0904293106.

Full text

APA, Harvard, Vancouver, ISO, and other styles

11

Muthusamy, Baby-Periyanayaki, Sumana Raychaudhuri, Paramasivam Natarajan, Fumiyoshi Abe, Ke Liu, William A. Prinz, and Todd R. Graham. "Control of Protein and Sterol Trafficking by Antagonistic Activities of a Type IV P-type ATPase and Oxysterol Binding Protein Homologue." Molecular Biology of the Cell 20, no. 12 (June 15, 2009): 2920–31. http://dx.doi.org/10.1091/mbc.e08-10-1036.

Full text

Abstract:

The oxysterol binding protein homologue Kes1p has been implicated in nonvesicular sterol transport in Saccharomyces cerevisiae. Kes1p also represses formation of protein transport vesicles from the trans-Golgi network (TGN) through an unknown mechanism. Here, we show that potential phospholipid translocases in the Drs2/Dnf family (type IV P-type ATPases [P4-ATPases]) are downstream targets of Kes1p repression. Disruption of KES1 suppresses the cold-sensitive (cs) growth defect of drs2Δ, which correlates with an enhanced ability of Dnf P4-ATPases to functionally substitute for Drs2p. Loss of Kes1p also suppresses a drs2-ts allele in a strain deficient for Dnf P4-ATPases, suggesting that Kes1p antagonizes Drs2p activity in vivo. Indeed, Drs2-dependent phosphatidylserine translocase (flippase) activity is hyperactive in TGN membranes from kes1Δ cells and is potently attenuated by addition of recombinant Kes1p. Surprisingly, Drs2p also antagonizes Kes1p activity in vivo. Drs2p deficiency causes a markedly increased rate of cholesterol transport from the plasma membrane to the endoplasmic reticulum (ER) and redistribution of endogenous ergosterol to intracellular membranes, phenotypes that are Kes1p dependent. These data suggest a homeostatic feedback mechanism in which appropriately regulated flippase activity in the Golgi complex helps establish a plasma membrane phospholipid organization that resists sterol extraction by a sterol binding protein.

APA, Harvard, Vancouver, ISO, and other styles

12

Bourne, A., K. Barnes, B. A. Taylor, A. J. Turner, and A. J. Kenny. "Membrane peptidases in the pig choroid plexus and on other cell surfaces in contact with the cerebrospinal fluid." Biochemical Journal 259, no. 1 (April 1, 1989): 69–80. http://dx.doi.org/10.1042/bj2590069.

Full text

Abstract:

A comprehensive survey of 11 peptidases, all of which are markers for renal microvillar membranes, has been made in membrane fractions prepared from pig choroid plexus. Two fractionation schemes were explored, both depending on a MgCl2-precipitation step, the preferred one having advantages in speed and yield of the activities. The specific activities of the peptidases in the choroid-plexus membranes were, with the exception of carboxypeptidase M, lower than in renal microvillar membranes: those of aminopeptidase N, peptidyl dipeptidase A (‘angiotensin-converting enzyme’) and gamma-glutamyltransferase were 3-5-fold lower, those of aminopeptidase A and endopeptidase-24.11 were 12-15 fold lower, and those of dipeptidyl peptidase IV and aminopeptidase W were 50-70-fold lower. Carboxypeptidase M had a similar activity in both membranes. Alkaline phosphatase and (Na+ + K+)-activated ATPase were more active in the choroid-plexus membranes. No activity for microsomal dipeptidase, aminopeptidase P and carboxypeptidase P could be detected. Six of the peptidases and (Na+ + K+)-activated ATPase were also studied by immunoperoxidase histochemistry at light- and electron-microscopic levels. Endopeptidase-24.11 and (Na+ + K+)-activated ATPase were uniquely located on the brush border, and the other two peptidases appeared to be much more abundant on the endothelial lining of microvessels. Dipeptidyl peptidase IV and aminopeptidase W were also detected in microvasculature. Pial membranes associated with the brain and spinal cord also stained positively for endopeptidase-24.11, aminopeptidase N and peptidyl dipeptidase A. The immunohistochemical studies indicated the subcellular fractionation did not discriminate between membranes derived from epithelial cells (i.e. microvilli) and those from endothelial cells. The possible significance of these studies in relation to neuropeptide metabolism and the control of cerebrospinal fluid production is discussed.

APA, Harvard, Vancouver, ISO, and other styles

13

Hurst, S. E., S. C. Minkin, J. Biggerstaff, and M. S. Dhar. "Transient Silencing of a Type IV P-Type ATPase,Atp10c, Results in Decreased Glucose Uptake in C2C12 Myotubes." Journal of Nutrition and Metabolism 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/152902.

Full text

Abstract:

Atp10cis a strong candidate gene for diet-induced obesity and type 2 diabetes. To identify molecular and cellular targets of ATP10C,Atp10cexpression was alteredin vitroin C2C12 skeletal muscle myotubes by transient transfection with anAtp10c-specific siRNA. Glucose uptake assays revealed that insulin stimulation caused a significant 2.54-fold decrease in 2-deoxyglucose uptake in transfected cells coupled with a significant upregulation of native mitogen-activated protein kinases (MAPKs), p38, and p44/42. Additionally, glucose transporter-1 (GLUT1) was significantly upregulated; no changes in glucose transporter-4 (GLUT4) expression were observed. The involvement of MAPKs was confirmed using the specific inhibitor SB203580, which downregulated the expression of native and phosphorylated MAPK proteins in transfected cells without any changes in insulin-stimulated glucose uptake. Results indicate thatAtp10cregulates glucose metabolism, at least in part via the MAPK pathway, and, thus, plays a significant role in the development of insulin resistance and type 2 diabetes.

APA, Harvard, Vancouver, ISO, and other styles

14

Shibata, Toshiaki, Hiroshi Hibino, Katsumi Doi, Toshihiro Suzuki, Yasuo Hisa, and Yoshihisa Kurachi. "Gastric type H+,K+-ATPase in the cochlear lateral wall is critically involved in formation of the endocochlear potential." American Journal of Physiology-Cell Physiology 291, no. 5 (November 2006): C1038—C1048. http://dx.doi.org/10.1152/ajpcell.00266.2006.

Full text

Abstract:

Cochlear endolymph has a highly positive potential of approximately +80 mV known as the endocochlear potential (EP). The EP is essential for hearing and is maintained by K+ circulation from perilymph to endolymph through the cochlear lateral wall. Various K+ transport apparatuses such as the Na+,K+-ATPase, the Na+-K+-2Cl− cotransporter, and the K+ channels Kir4.1 and KCNQ1/KCNE1 are expressed in the lateral wall and are known to play indispensable roles in cochlear K+ circulation. The gastric type of the H+,K+-ATPase was also shown to be expressed in the cochlear lateral wall (Lecain E, Robert JC, Thomas A, and Tran Ba Huy P. Hear Res 149: 147–154, 2000), but its functional role has not been well studied. In this study we examined the precise localization of H+,K+-ATPase in the cochlea and its involvement in formation of EP. RT-PCR analysis showed that the cochlea expressed mRNAs of gastric α1-, but not colonic α2-, and β-subunits of H+,K+-ATPase. Immunolabeling of an antibody specific to the α1 subunit was detected in type II, IV, and V fibrocytes distributed in the spiral ligament of the lateral wall and in the spiral limbus. Strong immunoreactivity was also found in the stria vascularis. Immunoelectron microscopic examination exhibited that the H+,K+-ATPase was localized exclusively at the basolateral site of strial marginal cells. Application of Sch-28080, a specific inhibitor of gastric H+,K+-ATPase, to the spiral ligament as well as to the stria vascularis caused prominent reduction of EP. These results may imply that the H+,K+-ATPase in the cochlear lateral wall is crucial for K+ circulation and thus plays a critical role in generation of EP.

APA, Harvard, Vancouver, ISO, and other styles

15

Debska-Slizien, A., P. Ho, R. Drangova, and A. D. Baines. "Endogenous renal dopamine production regulates phosphate excretion." American Journal of Physiology-Renal Physiology 266, no. 6 (June 1, 1994): F858—F867. http://dx.doi.org/10.1152/ajprenal.1994.266.6.f858.

Full text

Abstract:

We examined the effect of endogenous dopamine production on Pi and citrate excretion by Wistar rats. Carbidopa (20-40 mumol/kg ip) decreased dopamine, Pi, and citrate excretion within 20 min (86%, 47%, and 38%, respectively); Pi reabsorption increased 11 +/- 4% (P = 0.03). The decreases were sustained for at least 18 h. 3-Hydroxybenzylhydrazine (45 mumol/kg ip) reduced Pi excretion 24%. Benserazide (40 mumol/kg ip and 0.1 mumol/min iv) reduced dopamine excretion (94%) and blocked the effect of carbidopa on Pi and citrate excretion. In isolated perfused kidneys benserazide, carbidopa, and 3-hydroxybenzylhydrazine all decreased Pi excretion. Dopamine (1 mumol/l) added to cortical minceates reduced brush-border membrane vesicle (BBMV) 32P uptake by 8% (P < 0.02) and amiloride-inhibitable 22Na uptake by 19%. Carbidopa added to minceates increased 32P uptake by 12%. Carbidopa pretreatment increased (75%) amiloride-sensitive 22Na uptake into BBMV of rats fed a high-salt diet. Uptake was not increased into BBMV from rats fed a low-salt diet. Carbidopa increased (17%) basolateral membrane Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) gradually over 4 h. Na(+)-K(+)-ATPase did not increase in rats fed a low-phosphorous diet, but did increase when dopa was added to the diet. Thus endogenous dopamine appears to directly control Na(+)-Pi and Na+/H+ transport and secondarily alter basolateral membrane Na(+)-K(+)-ATPase.

APA, Harvard, Vancouver, ISO, and other styles

16

Dhar, Madhu S., Joshua S. Yuan, Sarah B. Elliott, and Carla Sommardahl. "A type IV P-type ATPase affects insulin-mediated glucose uptake in adipose tissue and skeletal muscle in mice." Journal of Nutritional Biochemistry 17, no. 12 (December 2006): 811–20. http://dx.doi.org/10.1016/j.jnutbio.2006.01.002.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

O'Brien, Peter James, C. David Ianuzzo, Gordon W. Moe, Terry P. Stopps, and Paul W. Armstrong. "Rapid ventricular pacing of dogs to heart failure: biochemical and physiological studies." Canadian Journal of Physiology and Pharmacology 68, no. 1 (January 1, 1990): 34–39. http://dx.doi.org/10.1139/y90-004.

Full text

Abstract:

Chronic, rapid ventricular pacing produces congestive heart failure in dogs. The objectives of this study were to determine whether or not (i) in vitro myocardial biochemical alterations reported for heart failure by volume or pressure overload also occurred with heart failure due to rate overload, and (ii) these biochemical alterations were related to relevant in vivo cardiac physiologic alterations. We compared 27 dogs that were paced to advanced heart failure with 21 sham-operated dogs. Dogs with heart failure had 55% lower left ventricular ejection fraction (22.5 ± 7.6 vs. 50.5 ± 5.1%) and cardiac index (81 ± 22 vs. 178 ± 48 mL∙min−1∙kg−1), 287% higher pulmonary capillary wedge pressure (27.5 ± 6.8 vs. 7.1 ± 3.4 mmHg; 1 mmHg = 133.3 Pa), and 64% greater left ventricular diastolic area (18.4 ± 3.7 vs. 11.2 ± 1.3 cm2) (all p < 0.05). Dogs with heart failure also had (i) 69% lower norepinephrine (232 ± 139 vs. 747 ± 220 ng/g protein), (ii) 25–50% lower activities of myofibrillar Ca ATPase (0.188 ± 0.026 vs. 0.253 ± 0.051 U/mg myofibrils), sarcoplasmic reticulum Ca-transport ATPase (0.155 ± 0.074 vs. 0.288 ± 0.043 U/mg membrane), and the glycolytic enzyme phosphofructokinase (33.4 ± 10.0 and 47.7 ± 15.8 U/g), (iii) 32% higher activity of the β-oxidation enzyme hydroxyacyl-CoA dehydrogenase (11.43 ± 1.48 vs. 8.67 ± 1.70 U/g), and (iv) 60% higher activity of Krebs cycle oxoglutarate dehydrogenase (2.89 ± 0.77 vs. 1.81 ± 0.95 U/g) (all p < 0.05). No differences between groups were observed for isozyme patterns and ATPase activity of myosin. The pacing-induced alterations in left ventricular norepinephrine and sarcoplasmic reticular and myofibrillar Ca ATPase best correlated with in vivo physiological alterations. Biochemical alterations produced by rate overload were similar to those reported for volume or pressure overload.Key words: heart disease, chronic tachycardia, biochemical changes.

APA, Harvard, Vancouver, ISO, and other styles

18

Monakhov, A. R., O. M. Tsiroulnikova, T. A. Dzhanbekov, D. Dzhiner, I. E. Pashkova, N. P. Mozheiko, K. M. Khizroev, and S. V. Gautier. "Right lobe liver transplantation in patient with fulminant form of the Wilson’s disease from AB0-incompatible relative donor." Russian Journal of Transplantology and Artificial Organs 19, no. 2 (June 23, 2017): 41–46. http://dx.doi.org/10.15825/1995-1191-2017-2-41-46.

Full text

Abstract:

Wilson’s disease is a rare congenital disease caused by deficiency of the copper-transporting P-type ATPase-B enzyme. The course of disease varies widely from the latent form to the acute liver failure which is observed in 5% of Wilson’s disease cases. This clinical case represents experience of liver transplantation as the only curative treatment for patients with fulminant form of Wilson’s disease demonstrating excellent postoperative results. Living donor liver transplantation allows performing the operation in the shortest possible time which is necessary in acute liver failure. The plasmapheresis with plasma exchange AB (IV) allows preparing the patient for transplantation with incompatible blood group.

APA, Harvard, Vancouver, ISO, and other styles

19

Mansharamani, Malini, Aveline Hewetson, and Beverly S. Chilton. "Cloning and Characterization of an Atypical Type IV P-type ATPase That Binds to the RING Motif of RUSH Transcription Factors." Journal of Biological Chemistry 276, no. 5 (October 31, 2000): 3641–49. http://dx.doi.org/10.1074/jbc.m004231200.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Borges-Pereira, Lucas, Samantha J. Thomas, Amanda Laizy dos Anjos e Silva, Paula J. Bartlett, Andrew P. Thomas, and Célia R. S. Garcia. "The genetic Ca2+ sensor GCaMP3 reveals multiple Ca2+ stores differentially coupled to Ca2+ entry in the human malaria parasite Plasmodium falciparum." Journal of Biological Chemistry 295, no. 44 (August 26, 2020): 14998–5012. http://dx.doi.org/10.1074/jbc.ra120.014906.

Full text

Abstract:

Cytosolic Ca2+ regulates multiple steps in the host-cell invasion, growth, proliferation, and egress of blood-stage Plasmodium falciparum, yet our understanding of Ca2+ signaling in this endemic malaria parasite is incomplete. By using a newly generated transgenic line of P. falciparum (PfGCaMP3) that expresses constitutively the genetically encoded Ca2+ indicator GCaMP3, we have investigated the dynamics of Ca2+ release and influx elicited by inhibitors of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase pumps, cyclopiazonic acid (CPA), and thapsigargin (Thg). Here we show that in isolated trophozoite phase parasites: (i) both CPA and Thg release Ca2+ from intracellular stores in P. falciparum parasites; (ii) Thg is able to induce Ca2+ release from an intracellular compartment insensitive to CPA; (iii) only Thg is able to activate Ca2+ influx from extracellular media, through a mechanism resembling store-operated Ca2+ entry, typical of mammalian cells; and (iv) the Thg-sensitive Ca2+ pool is unaffected by collapsing the mitochondria membrane potential with the uncoupler carbonyl cyanide m-chlorophenyl hydrazone or the release of acidic Ca2+ stores with nigericin. These data suggest the presence of two Ca2+ pools in P. falciparum with differential sensitivity to the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase pump inhibitors, and only the release of the Thg-sensitive Ca2+ store induces Ca2+ influx. Activation of the store-operated Ca2+ entry–like Ca2+ influx may be relevant for controlling processes such as parasite invasion, egress, and development mediated by kinases, phosphatases, and proteases that rely on Ca2+ levels for their activation.

APA, Harvard, Vancouver, ISO, and other styles

21

Salami, A. T., A. D. Famurewa, T. P. Omayone, T. F. Iyiola, and S. B. Olaleye. "Chrysophyllum Albidum Accelerates Delayed Gastric Ulcer Healing in Rats Through Oxidative Stress Reversal and Proton Pump Inhibition." Nigerian Journal of Pharmaceutical Research 16, no. 2 (January 19, 2021): 163–75. http://dx.doi.org/10.4314/njpr.v16i2.7.

Full text

Abstract:

Background: Chrysophyllum albidum has been documented to exert its gastric ulcer (GU) healing activities by modulating blood inflammatory mediators, however, other probable in-vivo underlying mechanisms are still vague which this study sought to investigate.Materials and Methods: Male Wistar rats (120-130g) divided into 9 groups (n=15 for groups I-VII; n=5 for groups VIII & IX) viz: Groups I- positive control (DUnA); II and III–250 and 500mg/kg methanolic extract of C. albidum (MeCaB) bark respectively; IV, V and VI-100mg/kg fractions A, B and C respectively; VII–30mg/kg omeprazole; VIII-ulcerated untreated (baseline), IX-negative control. Chronic GU was induced experimentally and delayed using indomethacin with 14 days simultaneous drug treatment. Gastric ulcer score, mucin content, antioxidant and proton pump activities were evaluated by days 3, 7 and 14 of treatment. Data were expressed as Mean+SEM and P<0.05 was significant.Results: C. albidum and fractions treated groups significantly decreased gastric ulcer scores and lipid peroxidation compared with DUnA. Negative control, C. albidum and fraction treated groups significantly increased superoxide dismutase, catalase, glutathione levels and mucin content compared with DUnA group by days 3 and 7. C. albidum, Negative and baseline control groups significantly decreased H+K+ATPase activities compared with DUnA by day14.Conclusion: C. albidum and its fractions facilitated the healing of gastric ulcer, probably by enhanced antioxidant levels, mucin content and decreased gastric H+K+ATPase activity. Keywords: C. albidum and chromatographic fractions, gastric ulcer healing, mucin , antioxidant, H+/K+ATPase pump.

APA, Harvard, Vancouver, ISO, and other styles

22

Olaniyan, Olugbemi T., Abdulfatai O. Ojewale, Olugbenga O. Eweoya, Adetola A. Adedoyin, Olamide A. Adesanya, Azeez O. Adeoye, and Olatayo S. Okeniran. "Modulatory Role of Vitamin E on Proton Pump (ATPase) Activity of Cadmium Chloride-Induced Testicular Damage in Wistar Rats." BioMed Research International 2021 (February 1, 2021): 1–7. http://dx.doi.org/10.1155/2021/4615384.

Full text

Abstract:

Proton pumps are membrane-bound enzymes important in generating gradients that help in maintaining cellular ion homeostasis, cell membrane potential, water, and solute transport across the cell surface. This study investigated the modulatory role of vitamin E on proton pump activity and reproductive parameters in cadmium-induced testicular damage. Twenty (20) male Wistar rats weighing between 180 and 200 g were sorted into 4 groups of five rats each. Group I served as the control and was given normal saline orally, Group II rats were treated with a single dose of 2 mg/kg BW cadmium chloride (CdCl2) intraperitoneally, Group III rats were given 100 mg/kg BW of vitamin E orally, and Group IV rats were given 100 mg/kg BW of vitamin E orally for 30 days prior to intraperitoneal administration of single dose of 2 mg/kg BW of cadmium chloride. The rats were anaesthetized with diethyl ether, and blood samples were obtained for sex hormonal analysis; caudal epididymis was dissected for sperm count, motility, and viability, and the testis were homogenized for lipid peroxidation and proton pump (Na+/K+ ATPase, Ca2+ ATPase, and Mg2+ ATPase) activity. Proton pump activity was assayed spectrophotometrically using the Stewart method to determine the inorganic phosphate level. Histopathological changes of the testis were also studied. The group treated with CdCl2 showed a significant ( p < 0.05 ) decrease in proton pump activity, sperm count, and motility and a significant ( p < 0.05 ) increase in malondialdehyde level when compared with the control group. The CdCl2-treated group also showed decrease reproductive organ weights and hormonal levels and cause necrosis of spermatogonia lining the seminiferous tubules. Rats treated with vitamin E orally for 30 days prior to CdCl2 exposure showed improvement in proton pump activity, a significant ( p < 0.05 ) increase in sperm parameters and luteinizing hormonal level, and a decrease in the lipid peroxidation level as compared with the CdCl2 group. This study showed that vitamin E ameliorated the toxic effect of CdCl2 on proton pump activity in the testes, hence improving testicular integrity, structures, and functions.

APA, Harvard, Vancouver, ISO, and other styles

23

Hu, Guanggan, and James W. Kronstad. "A Putative P-Type ATPase, Apt1, Is Involved in Stress Tolerance and Virulence in Cryptococcus neoformans." Eukaryotic Cell 9, no. 1 (November 30, 2009): 74–83. http://dx.doi.org/10.1128/ec.00289-09.

Full text

Abstract:

ABSTRACT The export of virulence factors, such as the capsule polysaccharide, to the cell surface is a critical aspect of the pathogenicity of Cryptococcus neoformans. A view of capsule export via exocytosis and extracellular vesicles is emerging, but the molecular mechanisms underlying virulence factor transport pathways remain to be established. In this study, we characterized the APT1 gene, which encodes a predicted integral membrane P-type ATPase belonging to the type IV, Drs2 family of aminophospholipid translocases (flippases) (APTs). APTs maintain the phospholipid asymmetry that is critical in membrane fusion events for trafficking and in establishing cell polarity. Deletion of the APT1 gene resulted in phenotypes consistent with similar roles in C. neoformans. These included altered actin distribution, increased sensitivity to stress conditions (oxidative and nitrosative stress) and to trafficking inhibitors, such as brefeldin A and monensin, a reduction in exported acid phosphatase activity, and hypersensitivity to the antifungal drugs amphotericin B, fluconazole, and cinnamycin. However, there was no difference in growth, capsule size, or melanin production between the wild type and the apt1 mutant strains at either 30°C or 37°C. Despite the absence of an influence on these major virulence factors, Apt1 was required for survival during interactions with macrophages, and apt1 mutants exhibited attenuated virulence in a mouse inhalation model of cryptococcosis. Therefore, Apt1 contributes to virulence and the stress response in C. neoformans through apparent functions in membrane fusion and trafficking that do not influence the deposition of major virulence factors, such as capsule and melanin, outside the cell.

APA, Harvard, Vancouver, ISO, and other styles

24

Borremans, B., J. L. Hobman, A. Provoost, N. L. Brown, and D. van der Lelie. "Cloning and Functional Analysis of thepbr Lead Resistance Determinant of Ralstonia metallidurans CH34." Journal of Bacteriology 183, no. 19 (October 1, 2001): 5651–58. http://dx.doi.org/10.1128/jb.183.19.5651-5658.2001.

Full text

Abstract:

ABSTRACT The lead resistance operon, pbr, of Ralstonia metallidurans (formerly Alcaligenes eutrophus) strain CH34 is unique, as it combines functions involved in uptake, efflux, and accumulation of Pb(II). The pbr lead resistance locus contains the following structural resistance genes: (i) pbrT, which encodes a Pb(II) uptake protein; (ii)pbrA, which encodes a P-type Pb(II) efflux ATPase; (iii)pbrB, which encodes a predicted integral membrane protein of unknown function; and (iv) pbrC, which encodes a predicted prolipoprotein signal peptidase. Downstream ofpbrC, the pbrD gene, encoding a Pb(II)-binding protein, was identified in a region of DNA, which was essential for functional lead sequestration. Pb(II)-dependent inducible transcription of pbrABCD from the PpbrApromoter is regulated by PbrR, which belongs to the MerR family of metal ion-sensing regulatory proteins. This is the first report of a mechanism for specific lead resistance in any bacterial genus.

APA, Harvard, Vancouver, ISO, and other styles

25

Xu, Peng, Ryan D. Baldridge, Richard J. Chi, Christopher G. Burd, and Todd R. Graham. "Phosphatidylserine flipping enhances membrane curvature and negative charge required for vesicular transport." Journal of Cell Biology 202, no. 6 (September 9, 2013): 875–86. http://dx.doi.org/10.1083/jcb.201305094.

Full text

Abstract:

Vesicle-mediated protein transport between organelles of the secretory and endocytic pathways is strongly influenced by the composition and organization of membrane lipids. In budding yeast, protein transport between the trans-Golgi network (TGN) and early endosome (EE) requires Drs2, a phospholipid translocase in the type IV P-type ATPase family. However, downstream effectors of Drs2 and specific phospholipid substrate requirements for protein transport in this pathway are unknown. Here, we show that the Arf GTPase-activating protein (ArfGAP) Gcs1 is a Drs2 effector that requires a variant of the ArfGAP lipid packing sensor (+ALPS) motif for localization to TGN/EE membranes. Drs2 increases membrane curvature and anionic phospholipid composition of the cytosolic leaflet, both of which are sensed by the +ALPS motif. Using mutant forms of Drs2 and the related protein Dnf1, which alter their ability to recognize phosphatidylserine, we show that translocation of this substrate to the cytosolic leaflet is essential for +ALPS binding and vesicular transport between the EE and the TGN.

APA, Harvard, Vancouver, ISO, and other styles

26

Adachi, Shun, Yasuhiro Murakawa, and Sota Hiraga. "SecA defects are accompanied by dysregulation of MukB, DNA gyrase, chromosome partitioning and DNA superhelicity in Escherichia coli." Microbiology 160, no. 8 (August 1, 2014): 1648–58. http://dx.doi.org/10.1099/mic.0.077685-0.

Full text

Abstract:

Spatial regulation of nucleoids and chromosome-partitioning proteins is important for proper chromosome partitioning in Escherichia coli. However, the underlying molecular mechanisms are unknown. In the present work, we showed that mutation or chemical perturbation of secretory A (SecA), an ATPase component of the membrane protein translocation machinery, SecY, a component of the membrane protein translocation channel and acyl carrier protein P (AcpP), which binds to SecA and MukB, a functional homologue of structural maintenance of chromosomes protein (SMC), resulted in a defect in chromosome partitioning. We further showed that SecA is essential for proper positioning of the oriC DNA region, decatenation and maintenance of superhelicity of DNA. Genetic interaction studies revealed that the topological abnormality observed in the secA mutant was due to combined inhibitory effects of defects in MukB, DNA gyrase and Topo IV, suggesting a role for the membrane protein translocation machinery in chromosome partitioning and/or structural maintenance of chromosomes.

APA, Harvard, Vancouver, ISO, and other styles

27

De Los Rios Castillo, Daniela, Mariel Zarco-Zavala, Sofia Olvera-Sanchez, Juan Pablo Pardo, Oscar Juarez, Federico Martinez, Guillermo Mendoza-Hernandez, José J. García-Trejo, and Oscar Flores-Herrera. "Atypical Cristae Morphology of Human Syncytiotrophoblast Mitochondria." Journal of Biological Chemistry 286, no. 27 (May 13, 2011): 23911–19. http://dx.doi.org/10.1074/jbc.m111.252056.

Full text

Abstract:

Mitochondrial complexes I, III2, and IV from human cytotrophoblast and syncytiotrophoblast associate to form supercomplexes or respirasomes, with the following stoichiometries: I1:(III2)1 and I1:(III2)1–2:IV1–4. The content of respirasomes was similar in both cell types after isolating mitochondria. However, syncytiotrophoblast mitochondria possess low levels of dimeric complex V and do not have orthodox cristae morphology. In contrast, cytotrophoblast mitochondria show normal cristae morphology and a higher content of ATP synthase dimer. Consistent with the dimerizing role of the ATPase inhibitory protein (IF1) (García, J. J., Morales-Ríos, E., Cortés-Hernandez, P., and Rodríguez-Zavala, J. S. (2006) Biochemistry 45, 12695–12703), higher relative amounts of IF1 were observed in cytotrophoblast when compared with syncytiotrophoblast mitochondria. Therefore, there is a correlation between dimerization of complex V, IF1 expression, and the morphology of mitochondrial cristae in human placental mitochondria. The possible relationship between cristae architecture and the physiological function of the syncytiotrophoblast mitochondria is discussed.

APA, Harvard, Vancouver, ISO, and other styles

28

Guo, Zhongxin, Jinfeng Lu, Xianbing Wang, Binhui Zhan, Wanxiang Li, and Shou-Wei Ding. "Lipid flippases promote antiviral silencing and the biogenesis of viral and host siRNAs in Arabidopsis." Proceedings of the National Academy of Sciences 114, no. 6 (January 25, 2017): 1377–82. http://dx.doi.org/10.1073/pnas.1614204114.

Full text

Abstract:

Dicer-mediated processing of virus-specific dsRNA into short interfering RNAs (siRNAs) in plants and animals initiates a specific antiviral defense by RNA interference (RNAi). In this study, we developed a forward genetic screen for the identification of host factors required for antiviral RNAi in Arabidopsis thaliana. Using whole-genome sequencing and a computational pipeline, we identified aminophospholipid transporting ATPase 2 (ALA2) and the related ALA1 in the type IV subfamily of P-type ATPases as key components of antiviral RNAi. ALA1 and ALA2 are flippases, which are transmembrane lipid transporter proteins that transport phospholipids across cellular membranes. We found that the ala1/ala2 single- and double-mutant plants exhibited enhanced disease susceptibility to cucumber mosaic virus when the virus-encoded function to suppress RNAi was disrupted. Notably, the antiviral activity of both ALA1 and ALA2 was abolished by a single amino acid substitution known to inactivate the flippase activity. Genetic analysis revealed that ALA1 and ALA2 acted to enhance the amplification of the viral siRNAs by RNA-dependent RNA polymerase (RdRP) 1 (RDR1) and RDR6 and of the endogenous virus-activated siRNAs by RDR1. RNA virus replication by plant viral RdRPs occurs inside vesicle-like membrane invaginations induced by the recruitment of the viral RdRP and host factors to subcellular membrane microdomains enriched with specific phospholipids. Our results suggest that the phospholipid transporter activity of ALA1/ALA2 may be necessary for the formation of similar invaginations for the synthesis of dsRNA precursors of highly abundant viral and host siRNAs by the cellular RdRPs.

APA, Harvard, Vancouver, ISO, and other styles

29

Lainey, Elodie, Marie Sebert, Cyrielle Bouteloup, Carole Leroy, Sylvain Thepot, Maximilien Tailler, Lionel Ades, et al. "Erlotinib Antagonizes Efflux Via ABC Transporters and Decreases P-Gp Cell Surface Expression by Inhibiting SRC Kinase and mTOR Pathways in Acute Myeloid Leukemia (AML)." Blood 118, no. 21 (November 18, 2011): 2564. http://dx.doi.org/10.1182/blood.v118.21.2564.2564.

Full text

Abstract:

Abstract Abstract 2564 Background: Erlotinib (Erlo) was originally developed as an epidermal growth factor receptor inhibitor, yet it also exerts antileukemic “off-target” effects, in vitro and in vivo in MDS and AML (Boehrer et al., Blood, 2008). In a preliminary pre-clinical study, we observed that Erlo increased chemosensitivity to current AML drugs in different AML cell lines and in ex vivo AML patient cells (n=3) (ASH 2010, 2163). Those first results suggested an implication of ABC-transporters in the potentiation of apoptosis. Here, we bring direct evidence for Erlo's ability to hinder efflux pumps and to decrease their expression on AML cells. Methods: Drug efflux via ABC-transporters (substrate: mitoxantrone-MTZ or doxorubicin-Dox), and specific efflux via P-gp (substrates: DioC23 and Rho-123), MRP (s: Calcein and CDCFDA) and BCRP (s: Hoechst 33342) were quantified by FACS following incubation with 10mM Erlo. Intracellular VP-16) content was quantified by Rapid Resolution Liquid Chromatography (RRLC). Biochemical inhibitors of the respective ABC-transporters (CSA (1μM), verapamil (Vera-10μM), MK571 (10μM), KO143 (500nM) served as positive controls. To assess chemosensitivity, 10mM Erlo was combined to AraC (100nM), Dox (100nM), or VP-16 (1mM) and apoptosis over-time (24, 48, 72h) quantified by DioC3(6)/PI staining. Assessment of sensitivity to the drug combinations listed above were carried out in KG-1 cells, and its more immature variant KG-1a and in ex vivo CD34+ marrow cells from AML patients (AML post MDS n=5, de novo AML n=5). P-gp's ATPase activity was quantified with the luminescence-based Pgp-Gloä Assay System. Surface expression of P-gp was determined by FACS analysis and total protein expression of MRP, BCRP and P-gp by immunoblot analysis. Functional relevance of signaling pathways was tested using the SRC inhibitor PP2 (10μM) and the mTOR inhibitor Rapamicin (10nM). Results: We found that I) Erlo inhibited efflux via P-gp, MRP and BCRP as demonstrated by increased intracellular retention of DioC23/Rho-123, Calcein/CDCFDA and Hoechst 33342, respectively, andby its ability to retain MTX (300nM) and Dox (200nM) intracellularly II) Inhibition of drug efflux was higher in KG-1 than in KG-1a cellss, in agreement with a lower expression of P-gp and BCRP on KG-1a as compared to KG-1 cells; III) Quantification of VP-16 by RRLC after incubation with or without Erlo showed the ability of Erlo to increase intracellular VP-16 contents by approximately 60%; IV) Erlo increased ATPase activity in a dose-dependant manner, supporting the notion that Erlo is a competitive inhibitor of P-gp; IV) Erlo combined to VP-16 induced synergistic effects on apoptosis in KG-1 cells, and to a lesser extent in KG-1a (48h KG-1: Erlo 20%, VP-16 38%, Erlo+VP16 78%, KG-1a 48h: Erlo 10%, VP-16: 12%, Erlo+VP16: 35%); V) 48h of incubation with Erlo reduced cell surface expression of P-gp in KG-1 cells by 50%, whereas total P-gp protein expression remained unchanged, suggesting that Erlo interferes exclusively with the protein form expressed on the cell surface, VI) Decrease of P-gp cell surface expression was recapitulated upon incubation with PP2 (10μM) or Rapamicin (10nM); VII) the combination of Erlo+VP-16 in 10 AML-patient samples induced synergistic effects on apoptosis in 5 of them and additive effects in 3 of them. Conclusions: We here confirm that Erlo increases sensitivity towards chemotherapeutic agents subjected to drug efflux via ABC-transporters and delineate the molecular pathways conveying these effects. Disclosures: Fenaux: Celgene: Honoraria, Research Funding.

APA, Harvard, Vancouver, ISO, and other styles

30

Greene, Nicholas P., James D. Fluckey, Brad S. Lambert, Elizabeth S. Greene, Steven E. Riechman, and Stephen F. Crouse. "Regulators of blood lipids and lipoproteins? PPARδ and AMPK, induced by exercise, are correlated with lipids and lipoproteins in overweight/obese men and women." American Journal of Physiology-Endocrinology and Metabolism 303, no. 10 (November 15, 2012): E1212—E1221. http://dx.doi.org/10.1152/ajpendo.00309.2012.

Full text

Abstract:

PPARδ is a transcription factor regulating the expression of genes involved in oxidative metabolism, which may regulate blood cholesterols through transcription of oxidative and lipoprotein metabolism genes. To determine the association of skeletal muscle PPARδ content with blood lipids and lipoproteins before and following exercise, overweight and obese men ( n = 9) and women ( n = 7) were recruited; age, BMI, body fat percentage, and V̇o2max were (means ± SE) 45 ± 2.5 yr, 31.9 ± 1.4 kg/m−2, 41.1 ± 1.5%, and 26.0 ± 1.3 mLO2·kg−1·min−1, respectively. Subjects performed 12 wk of endurance exercise training (3 sessions/wk, progressing to 500 kcal/session). To assess the acute exercise response, subjects performed a single exercise session on a treadmill (70% V̇o2max, 400 kcal energy expenditure) before and after training. Muscle and blood samples were obtained prior to any exercise and 24 h after each acute exercise session. Muscle was analyzed for protein content of PPARδ, PPARα, PGC-1α, AMPKα, and the oxidative and lipoprotein markers FAT/CD36, CPT I, COX-IV, LPL, F1 ATPase, ABCAI, and LDL receptor. Blood was assessed for lipids and lipoproteins. Repeated-measures ANOVA revealed no influence of sex on measured outcomes. PPARδ, PGC-1α, FAT/CD36, and LPL content were enhanced following acute exercise, whereas PPARα, AMPKα, CPT I, and COX-IV content were enhanced only after exercise training. PPARδ content negatively correlated with total and LDL cholesterol concentrations primarily in the untrained condition ( r ≤ −0.4946, P < 0.05), whereas AMPKα was positively correlated with HDL cholesterol concentrations regardless of exercise ( r ≥ 0.5543, P < 0.05). Our findings demonstrate exercise-induced expression of skeletal muscle PPARs and their target proteins, and this expression is associated with improved blood lipids and lipoproteins in obese adults.

APA, Harvard, Vancouver, ISO, and other styles

31

Winther-Larsen, Hanne C., Matthew C. Wolfgang, Jos P. M. van Putten, Norbert Roos, Finn Erik Aas, Wolfgang M. Egge-Jacobsen, Berenike Maier, and Michael Koomey. "Pseudomonas aeruginosa Type IV Pilus Expression in Neisseria gonorrhoeae: Effects of Pilin Subunit Composition on Function and Organelle Dynamics." Journal of Bacteriology 189, no. 18 (June 15, 2007): 6676–85. http://dx.doi.org/10.1128/jb.00407-07.

Full text

Abstract:

ABSTRACT Type IV pili (TFP) play central roles in the expression of many phenotypes including motility, multicellular behavior, sensitivity to bacteriophages, natural genetic transformation, and adherence. In Neisseria gonorrhoeae, these properties require ancillary proteins that act in conjunction with TFP expression and influence organelle dynamics. Here, the intrinsic contributions of the pilin protein itself to TFP dynamics and associated phenotypes were examined by expressing the Pseudomonas aeruginosa PilAPAK pilin subunit in N. gonorrhoeae. We show here that, although PilAPAK pilin can be readily assembled into TFP in this background, steady-state levels of purifiable fibers are dramatically reduced relative those of endogenous pili. This defect is due to aberrant TFP dynamics as it is suppressed in the absence of the PilT pilus retraction ATPase. Functionally, PilAPAK pilin complements gonococcal adherence for human epithelial cells but only in a pilT background, and this property remains dependent on the coexpression of both the PilC adhesin and the PilV pilin-like protein. Since P. aeruginosa pilin only moderately supports neisserial sequence-specific transformation despite its assembly proficiency, these results together suggest that PilAPAK pilin functions suboptimally in this environment. This appears to be due to diminished compatibility with resident proteins essential for TFP function and dynamics. Despite this, PilAPAK pili support retractile force generation in this background equivalent to that reported for endogenous pili. Furthermore, PilAPAK pili are both necessary and sufficient for bacteriophage PO4 binding, although the strain remains phage resistant. Together, these findings have significant implications for TFP biology in both N. gonorrhoeae and P. aeruginosa.

APA, Harvard, Vancouver, ISO, and other styles

32

Cabrera, Jesús A., Elizabeth A. Ziemba, Robert Colbert, Lorraine B. Anderson, Willem Sluiter, Dirk J. Duncker, Tammy A. Butterick, et al. "Altered expression of mitochondrial electron transport chain proteins and improved myocardial energetic state during late ischemic preconditioning." American Journal of Physiology-Heart and Circulatory Physiology 302, no. 10 (May 15, 2012): H1974—H1982. http://dx.doi.org/10.1152/ajpheart.00372.2011.

Full text

Abstract:

Altered expression of mitochondrial electron transport proteins has been shown in early preconditioned myocardial tissue. We wished to determine whether these alterations persist in the Second Window of Protection (SWOP) and if so, whether a favorable energetic state is facilitated during subsequent ischemia. Fourteen pigs underwent a SWOP protocol with ten 2-minute balloon inflations in the LAD artery, each separated by 2 minutes reperfusion. Twenty-four hours later, mitochondria were isolated from SWOP and SHAM pig hearts and analyzed for uncoupling protein (UCP)-2 content by western blot analysis, proteomic changes by iTRAQ® and respiration by an oxygen electrode. In parallel in vivo studies, high-energy nucleotides were obtained by transmural biopsy from anesthetized SWOP and SHAM pigs at baseline and during sustained low-flow ischemia. Compared with SHAM mitochondria, ex vivo SWOP heart tissue demonstrated increased expression of UCP-2, Complex IV (cytochrome c oxidase) and Complex V (ATPase) proteins. In comparison with SHAM pigs during in vivo conditions, transmural energetics in SWOP hearts, as estimated by the free energy of ATP hydrolysis (ΔG0), were similar at baseline but had decreased by the end of low-flow ischemia (-57.0 ± 2.1 versus -51.1 ± 1.4 kJ/mol; P < 0.05). In conclusion, within isolated mitochondria from preconditioned SWOP hearts, UCP-2 is increased and in concert with enhanced Complex IV and V proteins, imparts a favorable energetic state during low-flow ischemia. These data support the notion that mitochondrial adaptations that may reduce oxidant damage do not reduce the overall efficiency of energetics during sustained oxygen deprivation.

APA, Harvard, Vancouver, ISO, and other styles

33

Li, Xiao C., Gary E. Shull, Elisa Miguel-Qin, and Jia L. Zhuo. "Role of the Na+/H+ exchanger 3 in angiotensin II-induced hypertension." Physiological Genomics 47, no. 10 (October 2015): 479–87. http://dx.doi.org/10.1152/physiolgenomics.00056.2015.

Full text

Abstract:

The renal mechanisms responsible for angiotensin II (ANG II)-induced hypertension remain incompletely understood. The present study tested the hypothesis that the Na+/H+ exchanger 3 (NHE3) is required for ANG II-induced hypertension in mice. Five groups of wild-type ( Nhe3 +/+) and Nhe3 −/− mice were treated with vehicle or high pressor doses of ANG II (1.5 mg/kg/day ip, via minipump for 2 wk, or 10 pmol/min iv for 30 min). Under basal conditions, Nhe3 −/− mice had significantly lower systolic blood pressure (SBP) and mean intra-arterial pressure (MAP) ( P < 0.01), 24 h urine ( P < 0.05), urinary Na+ ( P < 0.01) and urinary K+ excretion ( P < 0.01). In response to ANG II, SBP and MAP markedly increased in Nhe3 +/+ mice in a time-dependent manner, as expected ( P < 0.01). However, these acute and chronic pressor responses to ANG II were significantly attenuated in Nhe3 −/− mice ( P < 0.01). Losartan blocked ANG II-induced hypertension in Nhe3 +/+ mice but induced marked mortality in Nhe3 −/− mice. The attenuated pressor responses to ANG II in Nhe3 −/− mice were associated with marked compensatory humoral and renal responses to genetic loss of intestinal and renal NHE3. These include elevated basal plasma ANG II and aldosterone and kidney ANG II levels, salt wasting from the intestines, increased renal AQP1, Na+/HCO3−, and Na+/K+-ATPase expression, and increased PKCα, mitogen-activated protein kinases ERK1/2, and glycogen synthase kinase 3αβ signaling proteins in the proximal tubules ( P < 0.01). We concluded that NHE3 in proximal tubules of the kidney, along with NHE3 in intestines, is required for maintaining basal blood pressure as well as the full development of ANG II-induced hypertension.

APA, Harvard, Vancouver, ISO, and other styles

34

PARKIN, Edward T., Anthony J. TURNER, and Nigel M. HOOPER. "Isolation and characterization of two distinct low-density, Triton-insoluble, complexes from porcine lung membranes." Biochemical Journal 319, no. 3 (November 1, 1996): 887–96. http://dx.doi.org/10.1042/bj3190887.

Full text

Abstract:

The Triton-insoluble complex from porcine lung membranes has been separated into two distinct subfractions visible as discrete light-scattering bands following buoyant density-gradient centrifugation in sucrose. Both of these detergent-insoluble complexes were enriched in the glycosyl-phosphatidylinositol (GPI)-anchored ectoenzymes alkaline phosphatase, aminopeptidase P and 5´-nucleotidase, and both complexes excluded the polypeptide-anchored ectoenzymes angiotensin-converting enzyme, dipeptidyl peptidase IV and aminopeptidases A and N. The GPI-anchored proteins in both complexes were susceptible to release by phosphatidylinositol-specific phospholipase C. Both complexes were also enriched in cholesterol and glycosphingolipids, and in caveolin/VIP21, although only the higher-density fraction was enriched in the plasmalemmal caveolar marker proteins Ca2+-ATPase and the inositol 1,4,5-trisphosphate receptor. Among the annexin family of proteins, annexins I and IV were absent from the two detergent-insoluble complexes, annexin V was present in both, and annexins II and VI were only enriched in the higher-density fraction. When the metal chelator EGTA was present in the isolation buffers, annexins II and VI dissociated from the higher-density detergent-insoluble complex and only a single light-scattering band was observed on the sucrose gradient, at the same position as for the lower-density complex. In contrast, in the presence of excess calcium only a single detergent-insoluble complex was isolated from the sucrose gradients, at an intermediate density. Thus the detergent-insoluble membrane complex can be subfractionated on the basis of what appears to be calcium-dependent, annexin-mediated, vesicle aggregation into two distinct populations, only one of which is enriched in plasmalemmal caveolar marker proteins.

APA, Harvard, Vancouver, ISO, and other styles

35

Gamu, Daniel, Anton Trinh, Val A. Fajardo, Eric Bombardier, and A. Russell Tupling. "Sarcolipin expression is not required for the mitochondrial enzymatic response to physical activity or diet." Journal of Applied Physiology 122, no. 5 (May 1, 2017): 1276–83. http://dx.doi.org/10.1152/japplphysiol.00833.2016.

Full text

Abstract:

In mice, transgenic manipulation of Ca2+-handling proteins is sufficient to alter the metabolic phenotype of muscle. We have previously shown that ablation of sarcolipin (SLN), a regulatory protein and uncoupler of sarco(endo)plasmic reticulum Ca2+-ATPases, leads to excessive diet-induced obesity and glucose intolerance in mice. However, it is unclear how loss of SLN per se affects muscle oxidative capacity and the ability of mitochondria to adapt to physiological stimuli, such as exercise training or calorie overload. To address this question, Sln−/− and wild-type (WT) littermates were given access to voluntary running wheels or underwent a treadmill training protocol for 8 wk. Furthermore, a separate group of mice were given a high-fat diet (42% kcal from fat for 8 wk) to determine whether the excessively obese phenotype of Sln−/− mice is associated with altered oxidative capacity. While voluntary running was insufficient to elicit mitochondrial adaptations, treadmill-trained mice showed significant increases ( P < 0.05) in the maximal activities of succinate dehydrogenase (+11%), citrate synthase (+12%), cytochrome oxidase (COX: +17%), along with increased protein expression of cytochrome c (+34%) and COX IV (+28%), which were irrespective of SLN expression. Lastly, no changes in the activities of mitochondrial marker enzymes existed with high-fat feeding, regardless of genotype. Together, these findings indicate that SLN is not required for the regulation of oxidative capacity in response to physiological stress, namely exercise or caloric surfeit. NEW & NOTEWORTHY Sarcolipin (SLN) has gained considerable attention for its uncoupling role of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA). Because of SLN’s ability to alter both cellular energy use and cytosolic [Ca2+], the potential exists for a regulatory role of mitochondrial biogenesis. Herein, we show skeletal muscle oxidative capacity to be unaltered in mice lacking SLN following exercise training or high-fat feeding. Our results contrast with published studies of SLN-overexpressing mice, possibly owing to supraphysiological uncoupling of SERCA.

APA, Harvard, Vancouver, ISO, and other styles

36

Rossier, Ombeline, and Nicholas P. Cianciotto. "Type II Protein Secretion Is a Subset of the PilD-Dependent Processes That Facilitate Intracellular Infection byLegionella pneumophila." Infection and Immunity 69, no. 4 (April 1, 2001): 2092–98. http://dx.doi.org/10.1128/iai.69.4.2092-2098.2001.

Full text

Abstract:

ABSTRACT Previously, we had demonstrated that a Legionella pneumophila prepilin peptidase (pilD) mutant does not produce type IV pili and shows reduced secretion of enzymatic activities. Moreover, it displays a distinct colony morphology and a dramatic reduction in intracellular growth within amoebae and macrophages, two phenotypes that are not exhibited by a pilin (pilEL ) mutant. To determine whether thesepilD-dependent defects were linked to type II secretion, we have constructed two new mutants of L. pneumophila strain 130b. Mutations were introduced into either lspDE, which encodes the type II outer membrane secretin and ATPase, orlspFGHIJK, which encodes the pseudopilins. Unlike the wild-type and pilEL strains, bothlspDE and lspG mutants showed reduced secretion of six pilD-dependent enzymatic activities; i.e., protease, acid phosphatase, p-nitrophenol phosphorylcholine hydrolase, lipase, phospholipase A, and lysophospholipase A. However, they exhibited a colony morphology different from that of thepilD mutant, suggesting that their surfaces are distinct. The pilD, lspDE, and lspG mutants were similarly and greatly impaired for growth within Hartmannella vermiformis, indicating that the intracellular defect of the peptidase mutant in amoebae is explained by the loss of type II secretion. When assessed for infection of U937 macrophages, bothlsp mutants exhibited a 10-fold reduction in intracellular multiplication and a diminished cytopathic effect. Interestingly, thepilD mutant was clearly 100-fold more defective than the type II secretion mutants in U937 cells. These results suggest the existence of a novel pilD-dependent mechanism for promotingL. pneumophila intracellular infection of human cells.

APA, Harvard, Vancouver, ISO, and other styles

37

Lackner, Laura L., David M. Raskin, and Piet A. J. de Boer. "ATP-Dependent Interactions between Escherichia coli Min Proteins and the Phospholipid Membrane In Vitro." Journal of Bacteriology 185, no. 3 (February 1, 2003): 735–49. http://dx.doi.org/10.1128/jb.185.3.735-749.2003.

Full text

Abstract:

ABSTRACT Proper placement of the division apparatus in Escherichia coli requires pole-to-pole oscillation of the MinC division inhibitor. MinC dynamics involves a membrane association-dissociation cycle that is driven by the activities of the MinD ATPase and the MinE topological specificity factor, which themselves undergo coupled oscillatory localization cycles. To understand the biochemical mechanisms underlying Min protein dynamics, we studied the interactions of purified Min proteins with phospholipid vesicles and the role of ATP in these interactions. We show that (i) the ATP-bound form of MinD (MinD.ATP) readily associates with phospholipid vesicles in the presence of Mg2+, whereas the ADP-bound form (MinD.ADP) does not; (ii) MinD.ATP binds membrane in a self-enhancing fashion; (iii) both MinC and MinE can be recruited to MinD.ATP-decorated vesicles; (iv) MinE stimulates dissociation of MinD.ATP from the membrane in a process requiring hydrolysis of the nucleotide; and (v) MinE stimulates dissociation of MinC from MinD.ATP-membrane complexes, even when ATP hydrolysis is blocked. The results support and extend recent work by Z. Hu et al. (Z. Hu, E. P. Gogol, and J. Lutkenhaus, Proc. Natl. Acad. Sci. USA 99:6761-6766, 2002) and support models of protein oscillation wherein MinE induces Min protein dynamics by stimulating the conversion of the membrane-bound form of MinD (MinD.ATP) to the cytoplasmic form (MinD.ADP). The results also indicate that MinE-stimulated dissociation of MinC from the MinC-MinD.ATP-membrane complex can, and may, occur prior to hydrolysis of the nucleotide.

APA, Harvard, Vancouver, ISO, and other styles

38

Wu, Alexander T. H., Bashir Lawal, Li Wei, Ya-Ting Wen, David T. W. Tzeng, and Wen-Cheng Lo. "Multiomics Identification of Potential Targets for Alzheimer Disease and Antrocin as a Therapeutic Candidate." Pharmaceutics 13, no. 10 (September 24, 2021): 1555. http://dx.doi.org/10.3390/pharmaceutics13101555.

Full text

Abstract:

Alzheimer’s disease (AD) is the most frequent cause of neurodegenerative dementia and affects nearly 50 million people worldwide. Early stage diagnosis of AD is challenging, and there is presently no effective treatment for AD. The specific genetic alterations and pathological mechanisms of the development and progression of dementia remain poorly understood. Therefore, identifying essential genes and molecular pathways that are associated with this disease’s pathogenesis will help uncover potential treatments. In an attempt to achieve a more comprehensive understanding of the molecular pathogenesis of AD, we integrated the differentially expressed genes (DEGs) from six microarray datasets of AD patients and controls. We identified ATPase H+ transporting V1 subunit A (ATP6V1A), BCL2 interacting protein 3 (BNIP3), calmodulin-dependent protein kinase IV (CAMK4), TOR signaling pathway regulator-like (TIPRL), and the translocase of outer mitochondrial membrane 70 (TOMM70) as upregulated DEGs common to the five datasets. Our analyses revealed that these genes exhibited brain-specific gene co-expression clustering with OPA1, ITFG1, OXCT1, ATP2A2, MAPK1, CDK14, MAP2K4, YWHAB, PARK2, CMAS, HSPA12A, and RGS17. Taking the mean relative expression levels of this geneset in different brain regions into account, we found that the frontal cortex (BA9) exhibited significantly (p < 0.05) higher expression levels of these DEGs, while the hippocampus exhibited the lowest levels. These DEGs are associated with mitochondrial dysfunction, inflammation processes, and various pathways involved in the pathogenesis of AD. Finally, our blood–brain barrier (BBB) predictions using the support vector machine (SVM) and LiCABEDS algorithm and molecular docking analysis suggested that antrocin is permeable to the BBB and exhibits robust ligand–receptor interactions with high binding affinities to CAMK4, TOMM70, and T1PRL. Our results also revealed good predictions for ADMET properties, drug-likeness, adherence to Lipinskís rules, and no alerts for pan-assay interference compounds (PAINS) Conclusions: These results suggest a new molecular signature for AD parthenogenesis and antrocin as a potential therapeutic agent. Further investigation is warranted.

APA, Harvard, Vancouver, ISO, and other styles

39

Arashiki, Nobuto, Yuichi Takakuwa, Hiromi Ogura, Taiju Utsugisawa, Satoru Miyano, Seishi Ogawa, Seiji Kojima, Shouichi Ohga, Narla Mohandas, and Hitoshi Kanno. "ATP11C Encodes a Major Flippase in Human Erythrocyte and Its Genetic Defect Causes Congenital Non-Spherocytic Hemolytic Anemia." Blood 126, no. 23 (December 3, 2015): 2131. http://dx.doi.org/10.1182/blood.v126.23.2131.2131.

Full text

Abstract:

Abstract Flippases are members of the P-IV ATPase family of proteins, and contribute to localization of phosphatidylserine (PS) in inner leaflet by its ATP-dependent active transport from outer to inner leaflet of lipid bilayer of erythrocyte membranes. It is critical that erythrocytes maintain PS in the inner monolayer to ensure their 120-day survival in circulation since externalization of PS will be recognized as an eat-me signal, resulting in phagocytosis by splenic macrophages. In the present study, we identified that ATP11C gene encodes a major flippase in human erythrocytes. A 13 years-old boy was referred to our hospital for consultation for work up of an undiagnosed congenital hemolytic anemia. Since extensive biochemical and molecular analysis failed to identify hemoglobin, erythrocyte membranes and enzyme abnormalities for the pathogenesis of hemolysis, we performed the whole exome analysis by massively parallel sequencing. We identified that the proband is hemizyogous, and the mother is heterozygous for a missense mutation of ATP11C, c.1253C>A, corresponding to a single amino acid substitution, p.Thr418Asn. Flipping activity as measured by PS internalization was decreased to 10% in the red cells of the proband compared to a normal control, clearly demonstrating that ATP11C encodes a major flippase in the human erythrocyte membranes. The PS-positive erythrocytes were not significantly increased in the whole blood but only in the most dense senescent cells, suggesting that PS exposure did not occur until very late stages of lifespan. We showed that PS exposure mediated by Ca2+-stimulated phospholipid scrambling was not different between red cells of the proband and control. Taken together, our findings imply that suppressed scrambling activity rather than flippase activity is the major contributor to maintainance of PS in inner leaflet of normal red cells during their 120-day lifespan, and that PS exposure to cell surface as an 'eat-me' signal depends primarily on scramblase activity at the end of lifespan. Importantly, our study has enables us to identify the major flippase of human erythrocyte membrane. Disclosures No relevant conflicts of interest to declare.

APA, Harvard, Vancouver, ISO, and other styles

40

van der Velden, Lieke M., Stan F. J. van de Graaf, and Leo W. J. Klomp. "Biochemical and cellular functions of P4 ATPases." Biochemical Journal 431, no. 1 (September 14, 2010): 1–11. http://dx.doi.org/10.1042/bj20100644.

Full text

Abstract:

P4 ATPases (subfamily IV P-type ATPases) form a specialized subfamily of P-type ATPases and have been implicated in phospholipid translocation from the exoplasmic to the cytoplasmic leaflet of biological membranes. Pivotal roles of P4 ATPases have been demonstrated in eukaryotes, ranging from yeast, fungi and plants to mice and humans. P4 ATPases might exert their cellular functions by combining enzymatic phospholipid translocation activity with an enzyme-independent action. The latter could be involved in the timely recruitment of proteins involved in cellular signalling, vesicle coat assembly and cytoskeleton regulation. In the present review, we outline the current knowledge of the biochemical and cellular functions of P4 ATPases in the eukaryotic membrane.

APA, Harvard, Vancouver, ISO, and other styles

41

Baldridge, R. D., and T. R. Graham. "Two-gate mechanism for phospholipid selection and transport by type IV P-type ATPases." Proceedings of the National Academy of Sciences 110, no. 5 (January 9, 2013): E358—E367. http://dx.doi.org/10.1073/pnas.1216948110.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Baldridge, R. D., and T. R. Graham. "Identification of residues defining phospholipid flippase substrate specificity of type IV P-type ATPases." Proceedings of the National Academy of Sciences 109, no. 6 (January 20, 2012): E290—E298. http://dx.doi.org/10.1073/pnas.1115725109.

Full text

APA, Harvard, Vancouver, ISO, and other styles

43

Tanaka, Yoshiki, Natsuki Ono, Takahiro Shima, Gaku Tanaka, Yohei Katoh, Kazuhisa Nakayama, Hiroyuki Takatsu, and Hye-Won Shin. "The phospholipid flippase ATP9A is required for the recycling pathway from the endosomes to the plasma membrane." Molecular Biology of the Cell 27, no. 24 (December 2016): 3883–93. http://dx.doi.org/10.1091/mbc.e16-08-0586.

Full text

Abstract:

Type IV P-type ATPases (P4-ATPases) are phospholipid flippases that translocate phospholipids from the exoplasmic (or luminal) to the cytoplasmic leaflet of lipid bilayers. In Saccharomyces cerevisiae, P4-ATPases are localized to specific subcellular compartments and play roles in compartment-mediated membrane trafficking; however, roles of mammalian P4-ATPases in membrane trafficking are poorly understood. We previously reported that ATP9A, one of 14 human P4-ATPases, is localized to endosomal compartments and the Golgi complex. In this study, we found that ATP9A is localized to phosphatidylserine (PS)-positive early and recycling endosomes, but not late endosomes, in HeLa cells. Depletion of ATP9A delayed the recycling of transferrin from endosomes to the plasma membrane, although it did not affect the morphology of endosomal structures. Moreover, depletion of ATP9A caused accumulation of glucose transporter 1 in endosomes, probably by inhibiting their recycling. By contrast, depletion of ATP9A affected neither the early/late endosomal transport and degradation of epidermal growth factor (EGF) nor the transport of Shiga toxin B fragment from early/recycling endosomes to the Golgi complex. Therefore ATP9A plays a crucial role in recycling from endosomes to the plasma membrane.

APA, Harvard, Vancouver, ISO, and other styles

44

Takatsu, Hiroyuki, Gaku Tanaka, Katsumori Segawa, Jun Suzuki, Shigekazu Nagata, Kazuhisa Nakayama, and Hye-Won Shin. "Phospholipid Flippase Activities and Substrate Specificities of Human Type IV P-type ATPases Localized to the Plasma Membrane." Journal of Biological Chemistry 289, no. 48 (October 14, 2014): 33543–56. http://dx.doi.org/10.1074/jbc.m114.593012.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Takatsu, Hiroyuki, Gaku Tanaka, Katsumori Segawa, Jun Suzuki, Shigekazu Nagata, Kazuhisa Nakayama, and Hye-Won Shin. "Phospholipid flippase activities and substrate specificities of human type IV P-type ATPases localized to the plasma membrane." Journal of Biological Chemistry 291, no. 41 (October 7, 2016): 21421. http://dx.doi.org/10.1074/jbc.a114.593012.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Baldridge, Ryan D., Peng Xu, and Todd R. Graham. "Type IV P-type ATPases Distinguish Mono-versusDiacyl Phosphatidylserine Using a Cytofacial Exit Gate in the Membrane Domain." Journal of Biological Chemistry 288, no. 27 (May 24, 2013): 19516–27. http://dx.doi.org/10.1074/jbc.m113.476911.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Takar, Mehmet, Yannan Huang, and Todd R. Graham. "The PQ-loop protein Any1 segregates Drs2 and Neo1 functions required for viability and plasma membrane phospholipid asymmetry." Journal of Lipid Research 60, no. 5 (March 1, 2019): 1032–42. http://dx.doi.org/10.1194/jlr.m093526.

Full text

Abstract:

Membrane asymmetry is a key organizational feature of the plasma membrane. Type IV P-type ATPases (P4-ATPases) are phospholipid flippases that establish membrane asymmetry by translocating phospholipids, such as phosphatidylserine (PS) and phospatidylethanolamine, from the exofacial leaflet to the cytosolic leaflet. Saccharomyces cerevisiae expresses five P4-ATPases: Drs2, Neo1, Dnf1, Dnf2, and Dnf3. The inactivation of Neo1 is lethal, suggesting Neo1 mediates an essential function not exerted by the other P4-ATPases. However, the disruption of ANY1, which encodes a PQ-loop membrane protein, allows the growth of neo1Δ and reveals functional redundancy between Golgi-localized Neo1 and Drs2. Here we show Drs2 PS flippase activity is required to support neo1Δ any1Δ viability. Additionally, a Dnf1 variant with enhanced PS flipping ability can replace Drs2 and Neo1 function in any1Δ cells. any1Δ also suppresses drs2Δ growth defects but not the loss of membrane asymmetry. Any1 overexpression perturbs the growth of cells but does not disrupt membrane asymmetry. Any1 coimmunoprecipitates with Neo1, an association prevented by the Any1-inactivating mutation D84G. These results indicate a critical role for PS flippase activity in Golgi membranes to sustain viability and suggests Any1 regulates Golgi membrane remodeling through protein-protein interactions rather than a previously proposed scramblase activity.

APA, Harvard, Vancouver, ISO, and other styles

48

Segawa, Katsumori, Sachiko Kurata, and Shigekazu Nagata. "Human Type IV P-type ATPases That Work as Plasma Membrane Phospholipid Flippases and Their Regulation by Caspase and Calcium." Journal of Biological Chemistry 291, no. 2 (November 13, 2015): 762–72. http://dx.doi.org/10.1074/jbc.m115.690727.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Bevers, Edouard M., and Patrick L. Williamson. "Getting to the Outer Leaflet: Physiology of Phosphatidylserine Exposure at the Plasma Membrane." Physiological Reviews 96, no. 2 (April 2016): 605–45. http://dx.doi.org/10.1152/physrev.00020.2015.

Full text

Abstract:

Phosphatidylserine (PS) is a major component of membrane bilayers whose change in distribution between inner and outer leaflets is an important physiological signal. Normally, members of the type IV P-type ATPases spend metabolic energy to create an asymmetric distribution of phospholipids between the two leaflets, with PS confined to the cytoplasmic membrane leaflet. On occasion, membrane enzymes, known as scramblases, are activated to facilitate transbilayer migration of lipids, including PS. Recently, two proteins required for such randomization have been identified: TMEM16F, a scramblase regulated by elevated intracellular Ca2+, and XKR8, a caspase-sensitive protein required for PS exposure in apoptotic cells. Once exposed at the cell surface, PS regulates biochemical reactions involved in blood coagulation, and bone mineralization, and also regulates a variety of cell-cell interactions. Exposed on the surface of apoptotic cells, PS controls their recognition and engulfment by other cells. This process is exploited by parasites to invade their host, and in specialized form is used to maintain photoreceptors in the eye and modify synaptic connections in the brain. This review discusses what is known about the mechanism of PS exposure at the surface of the plasma membrane of cells, how actors in the extracellular milieu sense surface exposed PS, and how this recognition is translated to downstream consequences of PS exposure.

APA, Harvard, Vancouver, ISO, and other styles

50

Smiles, William J., Evelyn B. Parr, Vernon G. Coffey, Orly Lacham-Kaplan, John A. Hawley, and Donny M. Camera. "Protein coingestion with alcohol following strenuous exercise attenuates alcohol-induced intramyocellular apoptosis and inhibition of autophagy." American Journal of Physiology-Endocrinology and Metabolism 311, no. 5 (November 1, 2016): E836—E849. http://dx.doi.org/10.1152/ajpendo.00303.2016.

Full text

Abstract:

Alcohol ingestion decreases postexercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation is unknown. Autophagy is an intracellular “recycling” system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent (combined resistance- and endurance-based) exercise. In a randomized crossover design, eight physically active males completed three experimental trials of concurrent exercise with either postexercise ingestion of alcohol and carbohydrate (12 ± 2 standard drinks; ALC-CHO), energy-matched alcohol and protein (ALC-PRO), or protein (PRO) only. Muscle biopsies were taken at rest and 2 and 8 h postexercise. Select autophagy-related gene (Atg) proteins decreased compared with rest with ALC-CHO ( P < 0.05) but not ALC-PRO. There were parallel increases ( P < 0.05) in p62 and PINK1 commensurate with a reduction in BNIP3 content, indicating a diminished capacity for mitochondria-specific autophagy (mitophagy) when alcohol and carbohydrate were coingested. DNA fragmentation increased in both alcohol conditions ( P < 0.05); however, nuclear AIF accumulation preceded this apoptotic response with ALC-CHO only ( P < 0.05). In contrast, increases in the nuclear content of p53, TFEB, and PGC-1α in ALC-PRO were accompanied by markers of mitochondrial biogenesis at the transcriptional ( Tfam, SCO2, and NRF-1) and translational (COX-IV, ATPAF1, and VDAC1) level ( P < 0.05). We conclude that alcohol ingestion following exercise triggers apoptosis, whereas the anabolic properties of protein coingestion may stimulate mitochondrial biogenesis to protect cellular homeostasis.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'P-IV ATPase'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles