Peroxynitrite causes calcium efflux from mitochondria which is prevented by Cyclosporin A.
Superoxide reacts with nitric oxide to form peroxynitrite, a potent oxidising agent which may contribute to tissue damage in pathological situations such as inflammation and ischaemia/reperfusion. One mechanism by which oxidative stress damages tissues is the induction of a specific Cyclosporin A-sensitive mitochondrial calcium efflux pathway. Here we show that peroxynitrite induces calcium efflux from mammalian mitochondria and that this efflux is blocked by Cyclosporin A. These data suggest that disruption of mitochondrial calcium efflux may contribute to tissue damage when superoxide and nitric oxide are present together in vivo.
Packer
M A
MA
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Murphy
M P
MP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009566:Nitrates / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D009566:Nitrates; C039642:peroxynitric acid; D016572:Cyclosporine; D002118:Calcium