期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1832, 期 8, 页码 1334-1344出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2013.04.009
关键词
Ceramide; Metabolism; Mitochondrial dynamics; Ca2+; Cell death; Cardiomyocyte
资金
- CONICYT [Anillo ACT 1111, FONDAP 1501006]
- National Institutes of Health [HL097768, HL072016]
- American Heart Association [06552024]
- CONICYT, Chile
- FONDECYT [3110114]
- Bicentennial Program, CONICYT, CHILE
- [Red 120003]
Ceramides are important intermediates in the biosynthesis and degradation of sphingolipids that regulate numerous cellular processes, including cell cycle progression, cell growth, differentiation and death. In cardiomyocytes, ceramides induce apoptosis by decreasing mitochondrial membrane potential and promoting cytochrome-c release. Ca2+ overload is a common feature of all types of cell death. The aim of this study was to determine the effect of ceramides on cytoplasmic Ca2+ levels, mitochondrial function and cardiomyocyte death. Our data show that C-2-ceramide induces apoptosis and necrosis in cultured cardiomyocytes by a mechanism involving increased Ca2+ influx, mitochondrial network fragmentation and loss of the mitochondrial Ca2+ buffer capacity. These biochemical events increase cytosolic Ca2+ levels and trigger cardiomyocyte death via the activation of calpains. (C) 2013 Elsevier B.V. All rights reserved.
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