Ceramide Induces Release of Pro-Apoptotic Proteins from Mitochondria by Either a Ca2+-Dependent or a Ca2+-Independent Mechanism |
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Authors: | Marco Di Paola Patrizia Zaccagnino Grazia Montedoro Tiziana Cocco Michele Lorusso |
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Affiliation: | Institute of Biomembranes and Bioenergetics, Consiglio Nazionale delle Ricerche, Bari, Italy. |
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Abstract: | 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 C2- or C16-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 Ca2+ -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 C2-ceramide causes cytochrome c release through a Ca2+ -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 C2-ceramide. |
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Keywords: | Ceramide heart mitochondria apoptosis cytochrome c release AIF release |
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