| Peritoneal dialysate effluent during peritonitis induces human cardiomyocyte apoptosis by regulating the expression of GATA-4 and Bcl-2 families. | |
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MedLine Citation:
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PMID: 20625998 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiovascular event and infection are leading causes of death from peritoneal dialysis (PD). This study examined in vitro cellular mechanism for cardiotoxicity induced by PD-related peritonitis. Cultured human cardiomyocytes were treated with PD effluent (PDE) during peritonitis (PPDE), and effects of PPDE on cultured cardiomyocytes in terms of apoptosis, with expression its related genes assessed. Results showed PPDE treatment of cardiomyocyte leading to onset of apoptosis, as confirmed by phosphatidylserine exposure plus DNA fragmentation and damage. This apoptosis is mediated by reduced Bcl-2/Bax and Bcl-x(L)/Bax ratios, as well as reduced expression of GATA-4, an important cardiomyocyte survival factor, at the level of transcription. These changes activated pro-apoptotic pathways. PPDE treatment also inhibited ERK signals, contributing to cardiotoxicity. Our findings revealed that PPDE contains potent pro-apoptotic factors that regulate expression of GATA-4 and Bcl-2 families, inducing cultured cardiomyocyte apoptosis. This pinpoints a key role of apoptosis in PD-associated cardiovascular events, along with a potential therapeutic target. |
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Authors:
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Hsin-Hui Wang; Ping-Chun Li; Hsiao-Ju Huang; Tzong-Yann Lee; Ching-Yuang Lin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular physiology Volume: 226 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-10-27 Completed Date: 2010-12-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 94-102 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Division of Nephrology, Taipei Veterans General Hospital, Taipei, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Ascitic Fluid / physiology* Cell Survival Cells, Cultured Dose-Response Relationship, Drug Extracellular Signal-Regulated MAP Kinases / metabolism Female GATA4 Transcription Factor / genetics, metabolism* Gene Expression Regulation / drug effects Genes, bcl-2 / genetics Humans Male Middle Aged Multigene Family Myocytes, Cardiac / cytology, drug effects* Peritoneal Dialysis* Peritonitis / pathology, therapy Proto-Oncogene Proteins c-bcl-2 / genetics, metabolism* Signal Transduction bcl-2-Associated X Protein / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/GATA4 Transcription Factor; 0/GATA4 protein, human; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
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