Oxidative stress is responsible for mitochondrial permeability transition induction by salicylate in liver mitochondria.
The interaction of salicylate with the respiratory chain of liver mitochondria generates hydrogen peroxide and, most probably, other reactive oxygen species, which in turn oxidize thiol groups and glutathione. This oxidative stress, confirmed by the prevention of action by antioxidant agents, leads to the induction of the mitochondrial permeability transition in the presence of Ca2+. This phenomenon induces further increase of oxidative damage resulting in impairment of oxidative phosphorylation and beta-oxidation, cardinal features of Reye's syndrome in the liver. Mitochondrial permeability transition induction also induces the release of cytochrome c and apoptotic inducing factor from mitochondria, suggesting that salicylate also behaves as a pro-apoptotic agent. The reactive group of salicylate for inducing oxidative stress is the hydroxyl group which, by interacting with a Fe-S cluster of mitochondrial Complex I, the so-called N-2(Fe-S) center, produces reactive oxygen species.
Battaglia
Valentina
V
Dipartimento di Chimica Biologica, Universitá di Padova, Istituto di Neuroscienze del C.N.R., Unitá per lo studio delle Biomembrane, Viale G. Colombo 3, 35121 Padova, Italy.
Salvi
Mauro
M
Toninello
Antonio
A
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress; D010539:Permeability; D051381:Rats; D017382:Reactive Oxygen Species; D020156:Salicylic Acid / Q000633:toxicity*
D000890:Anti-Infective Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D020156:Salicylic Acid; D002118:Calcium