Ceramide Induces Release of Pro-Apoptotic Proteins from Mitochondria by Either a Ca 2+ -Dependent or a Ca 2+ -Independent Mechanism
Journal of bioenergetics and biomembranes(2004)
摘要
Several observations have been reported in the last years indicating that ceramide may activate the mitochondrial route of apoptosis. We show here that on addition of either C 2 - or C 16 -ceramide to mitochondria isolated from rat heart and suspended in a saline medium, release of cytochrome c and apoptosis-inducing factor (AIF) from the intermembrane space takes place. The release process is Ca 2+ -independent and is not inhibited by Cyclosporin A (CsA). For the protein release process to occur, the presence of an oxidizable substrate is required. When mitochondria are suspended in sucrose instead of potassium medium, only short chain C 2 -ceramide causes cytochrome c release through a Ca 2+ -dependent and CsA sensitive mitochondrial permeability transition (MPT) mechanism. The latter effect appears to be related to the membrane potential dissipating ability exhibited by short chain C 2 -ceramide.
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关键词
cytochrome c,potassium,membrane potential,mitochondrial permeability transition,apoptosis inducing factor
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