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

doi:10.1016/j.bbadis.2013.04.009

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

Universidad de Chile

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

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 language	English
Pages (from-to)	1334-1344
Number of pages	11
Journal	Biochimica et Biophysica Acta - Molecular Basis of Disease
Volume	1832
Issue number	8
DOIs	https://doi.org/10.1016/j.bbadis.2013.04.009
Publication status	Published - 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.

Funding

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.

Funders	Funder number
National Institutes of Health	HL097768
National Heart, Lung, and Blood Institute	R01HL072016
American Heart Association	06552024
Comisión Nacional de Investigación Científica y Tecnológica	ACT 1111
Fondo Nacional de Desarrollo Científico y Tecnológico	3110114
Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias	A.F.G.Q, Red 120003, 1501006

ASJC Scopus Subject Areas

Molecular Medicine
Molecular Biology

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10.1016/j.bbadis.2013.04.009

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Parra, V., Moraga, F., Kuzmicic, J., López-Crisosto, C., Troncoso, R., Torrealba, N., Criollo, A., Díaz-Elizondo, J., Rothermel, B. A., Quest, A. F. G., & Lavandero, S. (2013). Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1832(8), 1334-1344. https://doi.org/10.1016/j.bbadis.2013.04.009

Parra, V, Moraga, F, Kuzmicic, J, López-Crisosto, C, Troncoso, R, Torrealba, N, Criollo, A, Díaz-Elizondo, J, Rothermel, BA, Quest, AFG & Lavandero, S 2013, 'Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1832, no. 8, pp. 1334-1344. https://doi.org/10.1016/j.bbadis.2013.04.009

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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.",

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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.",

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Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death

Abstract

Bibliographical note

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ASJC Scopus Subject Areas

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