title: Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death.
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. Ca(2+) 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 Ca(2+) levels, mitochondrial function and cardiomyocyte death. Our data show that C2-ceramide induces apoptosis and necrosis in cultured cardiomyocytes by a mechanism involving increased Ca(2+) influx, mitochondrial network fragmentation and loss of the mitochondrial Ca(2+) buffer capacity. These biochemical events increase cytosolic Ca(2+) levels and trigger cardiomyocyte death via the activation of calpains.
authors.affiliation: Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Químicas y Farmacéuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Valentina
authors.initials: V
authors.lastname: Parra
authors.forename: Francisco
authors.initials: F
authors.lastname: Moraga
authors.forename: Jovan
authors.initials: J
authors.lastname: Kuzmicic
authors.forename: Camila
authors.initials: C
authors.lastname: López-Crisosto
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Troncoso
authors.forename: Natalia
authors.initials: N
authors.lastname: Torrealba
authors.forename: Alfredo
authors.initials: A
authors.lastname: Criollo
authors.forename: Jessica
authors.initials: J
authors.lastname: Díaz-Elizondo
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Rothermel
authors.forename: Andrew F G
authors.initials: AF
authors.lastname: Quest
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002518:Ceramides; D045304:Cytochromes c; D002154:Calpain; D020169:Caspases; D002118:Calcium