Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death

Valentina Parra, Francisco Moraga, Jovan Kuzmicic, Camila López-Crisosto, Rodrigo Troncoso, Natalia Torrealba, Alfredo Criollo, Jessica Díaz-Elizondo, Beverly A. Rothermel, Andrew F.G. Quest, Sergio Lavandero

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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 C2-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.

Original languageEnglish (US)
Pages (from-to)1334-1344
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1832
Issue number8
DOIs
StatePublished - Aug 2013

Bibliographical note

Funding Information:
This work was supported by CONICYT (grant Anillo ACT 1111 and FONDAP 1501006 to A.F.G.Q. and S.L.) and Red 120003 (to S.L. and A.F.G.Q), the National Institutes of Health ( HL097768 and HL072016 to B.A.R.) and the American Heart Association ( 06552024 to B.A.R.). We are thankful for the PhD fellowships from CONICYT, Chile to V.P, J.K, and N.T., as well as for the FONDECYT postdoctoral funding 3110114 to R.T. V.P. holds a Postdoctoral International fellowship from Bicentennial Program, CONICYT, CHILE. We finally thank Fidel Albornoz for his excellent technical assistance.

Keywords

  • Ca
  • Cardiomyocyte
  • Cell death
  • Ceramide
  • Metabolism
  • Mitochondrial dynamics

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