title: Sphingosine impairs mitochondrial function by opening permeability transition pore.
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.
authors.affiliation: EA 2689, CHRU and Université de Lille 2, IFR 114 IMPRT, Lille 59045, France.
authors.forename: Sidi Mohamed
authors.initials: SM
authors.lastname: Hassoun
authors.forename: Steve
authors.initials: S
authors.lastname: Lancel
authors.forename: Patrice
authors.initials: P
authors.lastname: Petillot
authors.forename: Brigitte
authors.initials: B
authors.lastname: Decoster
authors.forename: Raphael
authors.initials: R
authors.lastname: Favory
authors.forename: Philippe
authors.initials: P
authors.lastname: Marchetti
authors.forename: Remi
authors.initials: R
authors.lastname: Neviere
mesh_terms: 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*
chemical_list: D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D016572:Cyclosporine; D045304:Cytochromes c; D013110:Sphingosine; D002118:Calcium