Sphingosine impairs mitochondrial function by opening permeability transition pore.
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.
Hassoun
Sidi Mohamed
SM
EA 2689, CHRU and Université de Lille 2, IFR 114 IMPRT, Lille 59045, France.
Lancel
Steve
S
Petillot
Patrice
P
Decoster
Brigitte
B
Favory
Raphael
R
Marchetti
Philippe
P
Neviere
Remi
R
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D009200:Myocardial Contraction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013110:Sphingosine / Q000378:metabolism / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D016572:Cyclosporine; D045304:Cytochromes c; D013110:Sphingosine; D002118:Calcium