TY - JOUR
T1 - Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death
AU - Parra, Valentina
AU - Moraga, Francisco
AU - Kuzmicic, Jovan
AU - López-Crisosto, Camila
AU - Troncoso, Rodrigo
AU - Torrealba, Natalia
AU - Criollo, Alfredo
AU - Díaz-Elizondo, Jessica
AU - Rothermel, Beverly A.
AU - Quest, Andrew F G
AU - Lavandero, Sergio
N1 - 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.
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Ca
KW - Cardiomyocyte
KW - Cell death
KW - Ceramide
KW - Metabolism
KW - Mitochondrial dynamics
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U2 - 10.1016/j.bbadis.2013.04.009
DO - 10.1016/j.bbadis.2013.04.009
M3 - Article
C2 - 23602992
AN - SCOPUS:84877878529
SN - 0925-4439
VL - 1832
SP - 1334
EP - 1344
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 8
ER -