Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1832

Article

Parra, Valentina^1,2,3,4  Moraga, Francisco^1,2  Kuzmicic, Jovan^1,2  Lopez-Crisosto, Camila^1,2  Troncoso, Rodrigo^1,2  Torrealba, Natalia^1,2  Criollo, Alfredo^3,4  Diaz-Elizondo, Jessica^1,2  Rothermel, Beverly A.^3,4  Quest, Andrew F. G.^1,2  Lavandero, Sergio^1,2,3,4 

[1] Univ Chile, Fac Ciencias Quim & Farmaceut, Ctr Estudios Mol Celula, Santiago 8389100, Chile

[2] Univ Chile, Fac Med, Santiago 8389100, Chile

[3] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Cardiol Div, Dallas, TX 75390 USA

[4] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

关键词: Ceramide;    Metabolism;    Mitochondrial dynamics;    Ca2+;    Cell death;    Cardiomyocyte;   

DOI  :  10.1016/j.bbadis.2013.04.009

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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