Dihydroceramide hinders ceramide channel formation: Implications on apoptosis |
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Authors: | J Stiban D Fistere M Colombini |
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Institution: | (1) Department of Biology, University of Maryland, College Park, Maryland, 20742;(2) Department of Biology, University of Maryland, College Park, MD, 20742 |
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Abstract: | Early in apoptosis, ceramide levels rise and the mitochondrial outer membrane becomes permeable to small proteins. The self-assembly
of ceramide to form channels could be the means by which intermembrane space proteins are released to induce apoptosis. Dihydroceramide
desaturase converts dihydroceramide to ceramide. This conversion may be removing an inhibitor as well as generating a pro-apoptotic
agent. We report that both long and short chain dihydroceramides inhibit ceramide channel formation in mitochondria. One tenth
as much dihydroceramide was sufficient to inhibit the permeabilization of the outer membrane by about 95% (C2) and 51% (C16). Similar quantities inhibited the release of carboxyfluorescein from liposomes indicating that other mitochondrial components
are not necessary for the inhibition. The apoptogenic activity of ceramide may thus depend on the ceramide to dihydroceramide
ratio resulting in a more abrupt transition from the normal to the apoptotic state when the de novo pathway is used in mitochondria. |
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Keywords: | ceramide channels ceramide-induced apoptosis cytochrome c release de novo synthesis dihydroceramide liposomes mitochondria |
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