| L-carnitine reduces doxorubicin-induced apoptosis through a prostacyclin-mediated pathway in neonatal rat cardiomyocytes. | |
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MedLine Citation:
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PMID: 19552975 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND: Clinical use of doxorubicin is greatly limited by its severe cardiotoxic side effects. L-carnitine is a vitamin-like substance which has been successfully used in many cardiomyopathies, however, the intracellular mechanism(s) remain unclear. The objective of this study was set to evaluate the protective effect of L-carnitine on doxorubicin-induced cardiomyocyte apoptosis, and to explore its intracellular mechanism(s). METHODS: Primary cultured neonatal rat cardiomyocytes were treated with doxorubicin (1 µM) with or without pretreatment with L-carnitine (1-30 mM). Lactate dehydrogenase assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling staining, and flow cytometry measurement were used to assess cytotoxicity and apoptosis. Fluorescent probes 2',7'-dichlorofluorescein diacetate and chemiluminescence assay of superoxide production were used to detect the production of reactive oxygen species. Western blotting was used to evaluate the quantity of cleaved caspase-3, cytosol cytochrome c, and Bcl-x(L) expression. RESULTS: L-carnitine inhibited doxorubicin-induced reactive oxygen species generation and NADPH oxidase activation, reduced the quantity of cleaved caspase-3 and cytosol cytochrome c, and increased Bcl-x(L) expression, resulting in protecting cardiomyocytes from doxorubicin-induced apoptosis. In addition, L-carnitine was found to increase the prostacyclin (PGI(2)) generation in cardiomyocytes. The siRNA transfection for PGI(2) synthase significantly reduced L-carnitine-induced PGI(2) and L-carnitine's protective effect. Furthermore, blockade the potential PGI(2) receptors, including PGI(2) receptors (IP receptors), and peroxisome proliferator-activated receptors alpha and delta (PPARα and PPARδ), revealed that the siRNA-mediated blockage of PPARα considerably reduced the anti-apoptotic effect of L-carnitine. CONCLUSIONS: These findings suggest that L-carnitine protects cardiomyocytes from doxorubicin-induced apoptosis in part through PGI(2) and PPARα-signaling pathways, which may potentially protect the heart from the severe toxicity of doxorubicin. |
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Authors:
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Hung-Hsin Chao; Ju-Chi Liu; Hong-Jye Hong; Jia-Wei Lin; Cheng-Hsien Chen; Tzu-Hurng Cheng |
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Publication Detail:
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Type: Journal Article Date: 2009-06-23 |
Journal Detail:
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Title: International journal of cardiology Volume: 146 ISSN: 1874-1754 ISO Abbreviation: Int. J. Cardiol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8200291 Medline TA: Int J Cardiol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 145-52 Citation Subset: IM |
Copyright Information:
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Copyright © 2009 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Medicine, Taipei Medical University, Taipei, Taiwan, ROC; Department of Cardiac Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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