Sphingosine impairs mitochondrial function by opening permeability transition pore |
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Authors: | Hassoun Sidi Mohamed Lancel Steve Petillot Patrice Decoster Brigitte Favory Raphael Marchetti Philippe Neviere Remi |
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Institution: | EA 2689, CHRU and Université de Lille 2, IFR 114 IMPRT, Lille 59045, France. |
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Abstract: | Growing evidence suggest that, in the heart, sphingosine participates to contractile dysfunction by altering calcium transients and mitochondria function. However, mechanisms underlying sphingosine-induced cardiac mitochondria dysfunction are poorly understood. Here, we studied the effects of sphingosine on isolated cardiac mitochondria of either wild-type or Bcl-2 overexpressing transgenic mice. Sphingosine induced reductions in ADP-coupled respiration, membrane potential, mitochondrial cytochrome c content and ATP production, which were partially prevented by cyclosporine A and mitochondrial Bcl-2 overexpression. These data suggest that sphingosine promotes mitochondrial permeability transition pore opening, which may result in uncoupled respiration and participate in cardiac contractile dysfunction. |
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