| Decreased cardiolipin synthesis corresponds with cytochrome c release in palmitate-induced cardiomyocyte apoptosis. | |
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MedLine Citation:
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PMID: 11500520 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apoptosis has been identified recently as a component of many cardiac pathologies. However, the potential triggers of programmed cell death in the heart and the involvement of specific metabolic pathway(s) are less well characterized. Detachment of cytochrome c from the mitochondrial inner membrane is a necessary first step for cytochrome c release into the cytosol and initiation of apoptosis. The saturated long chain fatty acid, palmitate, induces apoptosis in rat neonatal cardiomyocytes and diminishes content of the mitochondrial anionic phospholipid, cardiolipin. These changes are accompanied by 1) acyl chain saturation of phosphatidic acid and phosphatidylglycerol, 2) large increases in the levels of these two phospholipids, and 3) a decline in cardiolipin synthesis. Although cardiolipin synthase activity is unchanged, saturated phosphatidylglycerol is a poor substrate for this enzyme. Under these conditions, decreased cardiolipin synthesis and release of cytochrome c are directly and significantly correlated. The results suggest that phosphatidylglycerol saturation and subsequent decreases in cardiolipin affect the association of cytochrome c with the inner mitochondrial membrane, directly influencing the pathway to cytochrome c release and subsequent apoptosis. |
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Authors:
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D B Ostrander; G C Sparagna; A A Amoscato; J B McMillin; W Dowhan |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2001-08-10 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 276 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2001 Oct |
Date Detail:
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Created Date: 2001-10-08 Completed Date: 2001-12-04 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 38061-7 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, University of Texas-Houston, Medical School, Houston, Texas 77030, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Apoptosis / drug effects* Cardiolipins / biosynthesis* Cells, Cultured Cytochrome c Group / metabolism* Mass Spectrometry Myocardium / cytology, enzymology, metabolism* Palmitic Acid / toxicity* Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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5P30CA47904-12/CA/NCI NIH HHS; GM56389/GM/NIGMS NIH HHS; HL10019/HL/NHLBI NIH HHS; HL10304/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cardiolipins; 0/Cytochrome c Group; 57-10-3/Palmitic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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