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Lama, Zoé. "Étude fonctionnelle d'inhibiteurs de kinases réprimant la réplication du virus de la rage". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS490.
Pełny tekst źródłaHowever the rabies viral cycle is fairly well described, the interactions with the cellular machinery are not. This thesis project aimed at identifying and characterizing the cellular signaling pathways involved in the establishment and progress of the viral cycle through the study of cellular kinases. Indeed, kinases are the main actors of these pathways and their effects on certain rabies proteins have already been reported. In order to identify kinases involved in the viral cycle, we screened a kinase inhibitor library for anti-viral activity using a recombinant rabies virus expressing the GFP fluorescent protein. This assay allowed us to isolate two kinase inhibitors that block rabies virus infection: Tyrphostin 9, an inhibitor of the receptor tyrosine kinase platelet-derived growth factor receptor (PDGF.R), and Rottlerin, a PKCδ inhibitor and mitochondrial uncoupler. We confirmed their anti-viral action in different cell types (fibroblast, glioblastoma, neuroblastoma, as well as primary neurons) and on different rabies strains (CVS and SAD-B19). Using various experimental approaches, we found that each inhibitor impairs an early stage of the viral cycle: the viral fusion and more specifically the endosomal acidification by Tyrphostin 9 and the viral replication step by Rottlerin. We observed that Tyrphostin 9 also caused disintegration of the Golgi apparatus. The inhibition of endosomal acidification could therefore result from this effect. Seeking for the mechanisms involved in Rottlerin’s effect, we evidenced that it is independent of PKCδ. Experiments with a well characterized mitochondrial uncoupler (CCCP), revealed that the Rottlerin anti-viral effect is rather due to its mitochondrial uncoupling function, which leads to a decrease of the cellular ATP level. This study allowed the identification of two kinase inhibitors with anti-viral effects acting on early stages of the rabies cycle. The cellular targets as well as the effect on the cellular functions during viral infection remain to be determined. In vivo studies could validate their use in therapeutics as anti-rabies agents
Sivanathan, Sivatharushan [Verfasser]. "Synthese enantiomerenreiner α-Hydroxycarbonsäuren, neuer Cyclooctadepsipeptide sowie Studien zur Totalsynthese von Rottlerin / Sivatharushan Sivanathan". Wuppertal : Universitätsbibliothek Wuppertal, 2015. http://d-nb.info/1076930166/34.
Pełny tekst źródłaHeineck, Lukas [Verfasser], i Christian [Akademischer Betreuer] Kurts. "Der Einfluss von Rottlerin auf T-Zellpräsentation und -aktivierung / Lukas Heineck ; Betreuer: Christian Kurts". Marburg : Philipps-Universität Marburg, 2019. http://d-nb.info/1199537519/34.
Pełny tekst źródłaJuneja, Manisha. "Novel insights into MACC1 transcriptional regulation for identifying small molecule MACC1 inhibitors to restrict colorectal cancer progression". Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2014. http://dx.doi.org/10.18452/17038.
Pełny tekst źródłaMACC1 has been reported as a prognostic biomarker for tumor progression and metastasis-free survival in CRC along with other solid tumors. It induces cell motility and proliferation in cell culture and metastasis in mouse models. Consequently, targeting MACC1 to intervene in tumor progression and metastasis formation holds a promising approach to treat CRC patients. We designed a strategy to inhibit MACC1 via targeting its transcription. We first identified MACC1 gene promoter by creating various promoter-luciferase constructs. We then established that transcription factors such as Ap-1, Sp1, C/EBPs and GIPC1 bind to the MACC1 promoter and govern MACC1 transcription, expression and thus motility in vitro and in CRC patients. Using a high throughput screening targeting the MACC1 promoter, we identified small molecule MACC1 inhibitors, Rottlerin and Lovastatin. These inhibitors specifically restricted endogenous MACC1 promoter leading to reduced MACC1 expression in a time- and concentration-dependent manner. In vitro functional assays demonstrated the impact of the small molecule inhibitors on retarding cell proliferation and motility. Both inhibitors restricted Sp1 levels and interfered with the binding of c-Jun to the MACC1 promoter, thereby inhibiting MACC1 transcription. The study further described the effect of Rottlerin on a CRC-xenografted mouse model. Daily treatment of xenografted mice with Rottlerin resulted in the inhibition of MACC1 expression in the primary tumor accompanied with the restricted tumor growth. To summarize, this is the first study unraveling the MACC1 promoter, its transcriptional regulation and identification of newly identified MACC1 inhibitors. In clinical settings, inhibition of MACC1 expression using these inhibitors might provide immense potential for the treatment of CRC patients who are at high risk for MACC1-induced metastasis linked to shorter survival.
Cordeiro, Thuany de Moura. "Efeitos da rottlerin na esquizogonia eritrocitária de Plasmodium falciparum e implementação e avaliação de teste in vitro por fluorescência de atividade antiplasmodial". reponame:Repositório Institucional da UnB, 2014. http://repositorio.unb.br/handle/10482/15666.
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A malária é uma doença infecciosa causada por protozoários Plasmodium spp. O P. falciparum é considerado o mais severo por ser o responsável pela maioria dos casos de morte causados pela doença. Devido ao rápido surgimento de cepas de P. falciparum resistentes às drogas antimalariais dá-se a importância de realizar um screening de compostos da biodiversidade, além de elucidar os mecanismos de ação de substâncias com comprovada ação antiplasmodial, como por exemplo, a rottlerin, um inibidor da proteína quinase C. As proteínas quinases desempenham um papel essencial em muitas funções celulares, o que as tornam alvos muito atraentes para o desenvolvimento de novas drogas. A metodologia considerada padrão ouro para avaliar a atividade antimalárica de drogas é o ensaio com incorporação de hipoxantina tritiada. No entanto, o alto custo, a adoção de medidas de segurança e a produção de lixo radioativo limitam a utilização desta técnica. Desta forma, os objetivos deste trabalho foram à implementação do teste de atividade antiplasmodial baseado em fluorescência com SYBR Green I®, avaliação da atividade antimalárica das subfrações cromatográficas de sílica-gel do extrato de acetato de etila de Qualea grandiflora, uma planta típica do Cerrado brasileiro, e avaliação dos efeitos da rottlerin no ciclo intra-eritrocitário do P. falciparum por métodos bioquímicos e citofluorimétricos. Três subfrações de Q. grandiflora apresentaram atividade antiplasmodial moderada, sem atividade citotóxica e hemolítica aparentes. Foi demonstrado o efeito da rottlerin, um potencial efetor da autofagia, sobre o ciclo eritrocitário de P. falciparum por citometria de fluxo. De fato, a análise da população enriquecida de esquizonte de P. falciparum em cultura tratada por rottlerin comparada com a não tratada revelou que houve inibição da diferenciação dos merozoítos, acarretando na morte rápida do parasito. A fim de entender quais eram os alvos proteicos de ação desta molécula, foi realizada uma análise proteômica comparativa preliminar por eletroforese bidimensional. Três proteínas, Heat Shock Protein 90 (HSP90), 3-fosfoglicerato quinase (3-PGK) e lactato desidrogenase (LDH), superexpressas na população de esquizontes não tratada com a rottlerin foram identificadas. Estas proteínas pertencem à classe de proteínas quinases ou possuem um domínio de interação com quinase. A HSP90 está envolvida no processo de enovelamento proteico com um papel fundamental no crescimento e desenvolvimento do parasito e, consequentemente, estudada como potencial alvo de droga antiplasmodial. A LDH e a 3-PGK são enzimas do metabolismo da glicose, e assim, potenciais alvos bem conhecidos para compostos antimaláricos devido à dependência deste parasito à glicólise para produção de energia. O estudo da biodiversidade do Cerrado pode contribuir para a descoberta de compostos antimalariais e a conservação deste bioma ameaçado. A não detecção das proteínas identificadas na presença de rottlerin pode estar relacionada à indução da autofagia na esquizogonia eritrocitária e constituem potenciais alvos de drogas antimaláricas. _______________________________________________________________________________________ ABSTRACT
Malaria is an infectious disease caused by Plasmodium spp protozoa. The P. falciparum is considered the most severe, since it is responsible for the majority of deaths related to this disease. Due to the rapid emergence of resistant strains of P. falciparum against antimalarial drugs, a great importance can be given to the screening of biodiversity compounds in addition to elucidate the mechanisms of action of substances with demonstrated antiplasmodial action such as rottlerin, an inhibitor of protein kinase C. Protein kinases play a pivotal role in many cellular functions, which make them very attractive targets for the development of new drugs. The methodology considered the gold standard for assessing antimalarial drug activity is the [3H]hypoxanthine incorporation assay. However, the high cost, adoption of safety regulations and the production of radioactive waste limit the application of this technique. Therefore, the objectives of this study were to implement the antiplasmodial activity test based on SYBR® Green I fluorescence, assessment of antimalarial activity of silica gel chromatographic subfractions of Qualea grandiflora ethyl acetate extract, a typical plant of the Brazilian Cerrado, and assessment of the rottlerin‟s effects in erythrocytic cycle of P. falciparum by biochemical and cytofluorimetric methods. Three subfractions of Q.grandiflora showed moderate antiplasmodial activity without apparent cytotoxic and hemolytic activities. It was demonstrated the effect of rottlerin, a potencial autophagy effector, on P. falciparum erythrocytic cycle by flow cytometry. In fact, analysis of the schizont enriched population of P. falciparum in rottlerin-treated culture compared to untreated ones revealed that there was an inhibition of merozoites differentiation, resulting in the rapid death of the parasite. In order to elucidate which proteins were the targets of rottlerin action, a preliminary comparative proteomic analysis by two-dimensional electrophoresis was performed. Three proteins, heat shock protein 90 (HSP90), 3- phosphoglycerate kinase (PGK-3) and lactate dehydrogenase (LDH), upregulated in schizont population non treated with rottlerin were identified. These proteins belong to the class of protein kinases or possess domains that interact with them. The HSP90 is involved in the protein folding process with a critic role in parasite growth and development, thus being studied as a potential target for antiplasmodial drugs. The 3- PGK and LDH are enzymes of glucose metabolism, hence well known potential targets for antimalarial compounds due to parasite dependence on glycolysis to produce energy. The study of Cerrado biodiversity can contribute to the discovery of antimalarial compounds and to the conservation of this threatened biome. The not detection of these proteins identified in the presence of rottlerin may be related to autophagy induction in erythrocytic schizogony and constitute potential targets for antimalarial drugs.
Nguyen, Khoa Thuy Diem. "Energy metabolism in the brain and rapid distribution of glutamate transporter GLAST in astrocytes". Thesis, The University of Sydney, 2008. http://hdl.handle.net/2123/3996.
Pełny tekst źródłaNguyen, Khoa Thuy Diem. "Energy metabolism in the brain and rapid distribution of glutamate transporter GLAST in astrocytes". University of Sydney, 2008. http://hdl.handle.net/2123/3996.
Pełny tekst źródłaGlutamate transporters play a role in removing extracellular excitatory neurotransmitter, L-glutamate into the cells. The rate of the uptake depends on the density of the transporters at the membrane. Some studies claimed that glutamate transporters could transit between the cytoplasm and the membrane on a time-scale of minutes. The present study examined the distribution of glutamate transporter GLAST predominantly expressed in rat cortical cultured astrocytes between the membrane and the cytoplasm by using deconvolution microscopy and then analyzing the images. The regulation of the distribution of GLAST was studied in the presence of glutamate transporter substrate (D-aspartate), purinergic receptor activators (α,β-methylene ATP, adenosine), neuroleptic drugs (clozapine, haloperidol), ammonia (hyperammonia) and Na+/K+-ATPase inhibitors (ouabain, digoxin and FCCP). It was demonstrated that the translocation of GLAST towards the plasma membrane was induced by D-aspartate, α,β-methylene ATP, adenosine, clozapine and ammonia (at 100 μM and very high concentrations of 10 mM). However, the inhibition of Na+/K+-ATPase activity had an opposite effect, resulting in redistribution of GLAST away from the membrane. It has previously been claimed that the membrane-cytoplasm trafficking of GLAST was regulated by phosphorylation catalysed by protein kinase C delta (PKC-delta). Involvement of this mechanism has, however, been put to doubt when rottlerin, a PKC-delta inhibitor, used to test the hypothesis showed to inhibit Na+/K+-ATPase-mediated uptake of Rb+, suggesting that rottlerin influenced the activity of Na+/K+-ATPase. As Na+/K+-ATPase converts ATP to energy and pumps Na+, K+ ions, thus helping to maintain normal electrochemical and ionic gradients across the cell membrane. Its inhibition also reduced D-aspartate transport and could impact on the cytoplasm-to-membrane traffic of GLAST molecules. Furthermore, rottlerin decreased the activity of Na+/K+-ATPase by acting as a mitochondrial inhibitor. The present study has focused on the inhibition of Na+/K+-ATPase activity by rottlerin, ouabain and digoxin in homogenates prepared from rat kidney and cultured astrocytes. The activity of Na+/K+-ATPase was measured by the absorption of inorganic phosphate product generated from the hydrolysis of ATP and the fluorescent transition of the dye RH421 induced by the movement of Na+/K+-ATPase. This approach has a potential to test whether the rottlerin effect on Na+/K+-ATPase is a direct inhibition of the enzyme activity. Rottlerin has been found to block the activity of Na+/K+-ATPase in a dose-dependent manner in both rat kidney and astrocyte homogenates. Therefore, rottlerin inhibited the activity of Na+/K+-ATPase directly in a cell-free preparation, thus strongly indicating that the effect was direct on the enzyme. In parallel experiments, ouabain and digoxin produced similar inhibitions of Na+/K+-ATPase activity in rat kidney while digoxin blocked the activity of Na+/K+-ATPase to a greater extent than ouabain in rat cortical cultured astrocytes. In a separate set of experiments, Na+/K+-ATPase in the astrocytic membrane was found to be unsaturated in E1(Na+)3 conformation in the presence of Na+ ions and this could explain the differences between the effects of digoxin and ouabain on the activity of Na+/K+-ATPase in rat astrocytes. In addition, it was found that at low concentrations of rottlerin, the activity of Na+/K+-ATPase was increased rather than inhibited. This effect was further investigated by studying rottlerin interactions with membrane lipids. The activity of Na+/K+-ATPase has been reported to be regulated by membrane lipids. The enzyme activity can be enhanced by increasing fluidity of the lipid membrane. I have, therefore, proposed that rottlerin binds to the membrane lipids and the effects of rottlerin on Na+/K+-ATPase are mediated by changes in the properties (fluidity) of the membrane. The hypothesis was tested by comparing rottlerin and a detergent, DOC (sodium deoxycholate), for their binding to the lipids by using a DMPC (1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine) monolayer technique. DOC has been shown to both increase and inhibit activity of Na+/K+-ATPase in a manner similar to that displayed by rottlerin. The effects of rottlerin and DOC on the DMPC monolayers were studied by measuring the surface pressure of DMPC monolayers and surface area per DMPC molecule. I established that both rottlerin and DOC decreased the surface pressure of DMPC monolayers and increased the surface area per DMPC molecule. This indicates that both rottlerin and DOC penetrated into the DMPC monolayers. If rottlerin can interact with the lipids, changes in fluidity of the lipid membrane cannot be ruled out and should be considered as a possible factor contributing to the effects of rottlerin on the activity of Na+/K+-ATPase. Overall, the study demonstrates that rottlerin is not only a PKC-delta inhibitor but can have additional effects, both on the enzyme activities (Na+/K+-ATPase) and/or on lipid-containing biological structures such as membranes. The findings have implication not only for studies where rottlerin was used as a supposedly specific PKC-delta inhibitor but also for mechanisms of its toxicity.
Contreras, Xavier. "Rôle des voies PKC et calcium dans les productions de TNF-alpha et d'IL-10 induites par la protéine Tat du Virus de l'immuodéficience humaine chez le monocyte humain et dans la réplication de virus R5-tropiques dans le macrophage". Toulouse 3, 2005. http://www.theses.fr/2005TOU30012.
Pełny tekst źródłaThe goals of this study are on the one hand the characterization of signaling pathways involved in TNF-a and IL-10 productions by human monocytes/macrophages stimulated by Tat protein of HIV-1 and on the other hand the evaluation of the role of these signaling pathways in viral replication. Thus, Tat protein activates the calcium and PKC pathways in the monocyte/macrophage to stimulate TNF-a and IL-10 productions via its 1-45 N-terminal domain. The 20-45 region stimulates calcium entry in monocytes via DHP-sensitive calcium channels. Tat induces the activation of a, bI, bII, d, and e PKC isozymes, but only d and bII PKC isozymes activation is essential for IL-10 production. The selective inhibition of PKC d activation by rottlerin blocks CCR5-tropic HIV-1 BaL virus replication in human macrophage by acting probably at the level of an early step of the virus life cycle involving the cytoskeleton
Koterba, Kristen L. "Regulation of Autophagy and Cell Death in Breast Carcinoma Cells". University of Toledo Health Science Campus / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=mco1276005638.
Pełny tekst źródłaRottler, Andreas [Verfasser]. "Investigation of Radial Metamaterials / Andreas Rottler". München : Verlag Dr. Hut, 2013. http://d-nb.info/1037286847/34.
Pełny tekst źródłaLakshmanan, Aparna. "Modulation of Sodium Iodide Symporter-mediated Thyroidal Radioiodide Uptake by Small Molecule Inhibitors, Natural Plant-based Products and microRNAs". The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429407914.
Pełny tekst źródłaRottler, Klemens [Verfasser], i Josef [Akademischer Betreuer] Jochum. "Muons in the CRESST Dark Matter Experiment / Klemens Rottler ; Betreuer: Josef Jochum". Tübingen : Universitätsbibliothek Tübingen, 2014. http://d-nb.info/1196801460/34.
Pełny tekst źródłaRottler, Philipp [Verfasser]. "Kortikale Reorganisation nach Hypoglossus-Fazialis Transfer bei Patienten mit peripherer Fazialisparese im Zusammenhang des klinischen Outcome / Philipp Rottler". Greifswald : Universitätsbibliothek Greifswald, 2014. http://d-nb.info/1052159338/34.
Pełny tekst źródłaSchneider, Ludwig [Verfasser], Marcus [Akademischer Betreuer] Müller, Marcus [Gutachter] Müller, Annette [Gutachter] Zippelius i Jörg [Gutachter] Rottler. "Rheology and Structure Formation in Complex Polymer Melts / Ludwig Schneider ; Gutachter: Marcus Müller, Annette Zippelius, Jörg Rottler ; Betreuer: Marcus Müller". Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2019. http://d-nb.info/118402104X/34.
Pełny tekst źródłaRottler, Sarah [Verfasser], i Michael [Akademischer Betreuer] Erhard. "Verhalten als Tierschutzindikator für die vergleichende Beurteilung einer Boden- und Kombihaltung für Mastkaninchen unter Praxisbedingungen / Sarah Rottler ; Betreuer: Michael Erhard". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1191098095/34.
Pełny tekst źródłaRottler, Erwin [Verfasser], Axel [Akademischer Betreuer] Bronstert, Gerd [Akademischer Betreuer] Bürger, Axel [Gutachter] Bronstert, Gerd [Gutachter] Bürger i Kerstin [Gutachter] Stahl. "Transient merging of two Rhine flow regimes from climate change / Erwin Rottler ; Gutachter: Axel Bronstert, Gerd Bürger, Kerstin Stahl ; Axel Bronstert, Gerd Bürger". Potsdam : Universität Potsdam, 2021. http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-517665.
Pełny tekst źródłaAraújo, Cristina Dias. "Atividade antibacteriana in vitro e in sito de Allium tuberosum - Rottler ex sprengl (alho "nirá" ou alho "japonês", "jiucai" ou alho "chinês") - liliaceae - sobre agentes de toxinfecções alimentares". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2007. http://hdl.handle.net/10183/10842.
Pełny tekst źródłaIt was looked for to identify and to compare the antibacterial activity of the alcoholic extract of three accesses of Allium tuberosum - Rottler ex Sprengl - Liliaceae - original from Porto Alegre (RS/BR) metropolitan area, confronted to alimentary toxic infections agents, specifically: Staphylococcus aureus (ATCC 25.923), Enterococcus faecalis (ATCC 19.433), Salmonella Enteritidis (ATCC 11.076) Escherichia coli (ATCC 11.229). Initially, in vitro, through Test of Dilution, System of Multiple Tubes and the use of bacterial uninhibitors, was determined the Intensity of the Activity of Bacterial Inhibition (IINIB) and the Intensity of Activity of Bacterial Inactivation (IINAB), being revealed selective capacities on the different Gram-negative inoculums, that reached inhibition and maximum and permanent inactivation for Salmonella at 48 hours of confrontation inoculum/extract, and 72 hours of confrontation for Escherichia coli. The Gram-positive bacteria (Staphylococcus and Enterococcus) presented total resistance in the different confrontations. There was not significant difference in the antibacterial activity of the three accesses of garlic in study. Subsequently, for one of the samples of garlic, through Test of Suspension, was determined IINAB in alimentary simulation of creamy cheese seasoned with alcoholic extract in final concentration of 10, 20 and 30%, assisting to the legislation as for to identification pattern and quality of this food; as well as in simulation of alimentary preparation of bouillon, with the plant recently picked, in the final concentration of 50%. In the model creamy cheese, E.coli was shown completely resistant in final concentrations of 103, 104 and 105 U.F.C./mL, these immediately above the maximum concentration tolerated by the Brazilian legislation, in three times of confrontation (24, 48, 72 hours), in all of the final concentrations of the alcoholic extract. In the conditions of the simulated bouillon, Salmonella was totally inactivated in the concentration of 105 U.F.C./mL already at 24 hours of confrontation, while Escherichia reached this point at 48 hours of confrontation. Is commented, likewise, the meaning of the demonstrated bacterial inhibition, related to the prediction of the results of bacteriological diagnosis in protocols of alimentary toxic infective outbreaks investigation.
Tian-YouLiao i 廖天佑. "The modulating effects of rottlerin on psychostimulant-induced conditioned place preference". Thesis, 2015. http://ndltd.ncl.edu.tw/handle/76401112620904555353.
Pełny tekst źródła國立成功大學
行為醫學研究所
103
Three cocaine (10 mg/kg/conditioning, COC)- and methamphetamine (1 mg/kg/conditioning, MA)-place conditionings reliably established the drug-induced conditioned place preference (CPP) in 8-week-old male C57BL/6 mice. An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 hrs prior to the first COC- and MA-place conditioning prevented the establishment of COC and MA-induced CPP. Following the establishment of the COC- and MA-induced CPP, three consecutive daily saline-place conditionings were used to extinguish mouse CPP performance. A single rottlerin injection (5 mg/kg, i.p.) 20 hrs prior to the first saline-place conditioning bout did not affect such conditionings-produced CPP extinction but diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP. Omitting the extinction conditionings, a single rottlerin injection (5 mg/kg) did not cause the conditionings-produced CPP extinction. A single rottlerin (5 mg/kg, i.p.) treatment produced fast-onset and long-lasting increases in hippocampal BDNF levels, while such a treatment did not alter ERK and CREB phosphorylation in the hippocampus. Pretreatment with a BDNF TrkB receptor antagonist, K252a (5 µg/kg), did not affect rottlerin’s suppressing effect on cocaine-induced CPP. Treatment with 7,8-dihydroxyflavone (10 mg/kg x 6), a selective TrkB agonist, prior to each conditioning bout did not affect COC-induced CPP. Based on these results, suggest that systemic rottlerin treatment may be beneficial in facilitating the erasure of COC and MA-supported memory. Importantly, such a treatment may afford a therapeutic advance in corroborating the extinction training-caused forgetting of the COC and MA-supported memory. However, rottlerin-produced brain BDNF increases play a negligible role in mediating its effects on the formation and maintenance of psychostimulant-supported memory in this regard.
Ya-Fan, Liao, i 廖雅芳. "Human ornithine decarboxylase prevents apoptosis by rottlerin in human leukemia HL60 cells". Thesis, 2003. http://ndltd.ncl.edu.tw/handle/77473494285300889940.
Pełny tekst źródła中山醫學大學
免疫學研究所
91
Ornithine decarboxylase (ODC), a rate-determining enzyme of the polyamine biosynthetic pathway, is involved in the control of cell cycle, differentiation, cell growth and apoptosis. Previous studies described that protein kinase Cd (PKCd) regulates ODC activity. In this thesis, human leukemia cell line, HL60 cell, was used for the treatment with a specific PKCd inhibitor, rottlerin, to measure the effects on cell growth. Our data are showed that apoptosis parameters including DNA fragmentation, nuclear morphological change and sub-G1 fraction, appeared after 24 h by 5 μM rottlerin treatment. Furthermore, rottlerin caused a decrease in 72% of ODC protein expression and an increase in threonine, rather than serine and tyrosine dephosphorylation on ODC enzyme compared with the control after incubation for 10 h. To determine whether ODC could down-regulate rottlerin-induced apoptosis, HL60 cells were stably transfected with ODC cDNA. HL60-ODC cells exhibited a 2.5-fold increase in ODC protein compared with vector only (HL60-pcDNA3) or HL60 cells. Restoration of ODC expression in the HL60-ODC cells resulted in rescue of rottlerin-induced apoptosis of HL60 cells. Simultaneously, phosphothreonine-ODC of rottlerin-treated HL60-ODC cells was highly elevated comparing with HL60-pcDNA3 cells. Taken together, we suggested that rottlerin, a PKCd inhibitor, might decrease phosphothreonine-ODC to reduce both protein stability and enzyme activity of ornithine decarbooxylase and finally resulted in cell apoptosis. Our results also revealed that elevation of ODC protein and phosphotheronine-ODC prevents apoptosis in rottlerin treated cells. This study provided for the first time a new and important linkage between programmed cell death and the regulation of the posttranslational modification of ODC.
Ming-HengHsiung i 熊明珩. "Involvement of different signaling pathways in mouse hippocampus in the modulatory effects of rottlerin and MK-801 on inhibitory avoidance memory". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/atbmfe.
Pełny tekst źródłaNevělíková, Leona. "Exprese PKC alfa v myokardu potkana adaptovaného na/ hronickou hypoxii: vliv chelerythrinu a rottlerinu". Master's thesis, 2006. http://www.nusl.cz/ntk/nusl-373671.
Pełny tekst źródłaRottler, Jessica [Verfasser]. "Lebensalter und endotheliale Dysfunktion: Veränderungen funktioneller, struktureller und biochemischer Kenngrößen der Endothelfunktion / vorgelegt von Jessica Rottler". 2005. http://d-nb.info/990489965/34.
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