Effect of ischemic preconditioning on mitochondrial dysfunction and mitochondrial p53 translocation after transient global cerebral ischemia in rats.
Transient global brain ischemia induces dysfunctions of mitochondria including disturbance in mitochondrial protein synthesis and inhibition of respiratory chain complexes. Due to capacity of mitochondria to release apoptogenic proteins, ischemia-induced mitochondrial dysfunction is considered to be a key event coupling cerebral blood flow arrest to neuronal cell death. Ischemic preconditioning (IPC) represents an important phenomenon of adaptation of central nervous system (CNS) to sub-lethal short-term ischemia, which results in increased tolerance of CNS to the lethal ischemia. In this study we have determined the effect of ischemic preconditioning on ischemia/reperfusion-associated inhibition of mitochondrial protein synthesis and activity of mitochondrial respiratory chain complexes I and IV in the hippocampus of rats. Global brain ischemia was induced by 4-vessel occlusion in duration of 15 min. Rats were preconditioned by 5 min of sub-lethal ischemia and 2 days later, 15 min of lethal ischemia was induced. Our results showed that IPC affects ischemia-induced dysfunction of hippocampal mitochondria in two different ways. Repression of mitochondrial translation induced during reperfusion of the ischemic brain is significantly attenuated by IPC. Slight protective effect of IPC was documented for complex IV, but not for complex I. Despite this, protective effect of IPC on ischemia/reperfusion-associated changes in integrity of mitochondrial membrane and membrane proteins were observed. Since IPC exhibited also inhibitory effect on translocation of p53 to mitochondria, our results indicate that IPC affects downstream processes connecting mitochondrial dysfunction to neuronal cell death.
Institute of Biochemistry, Jessenius Faculty of Medicine, Comenius University, Mala Hora 4, Martin 03601, Slovak Republic. racay@jfmed.uniba.sk
Peter
P
Racay
Zuzana
Z
Tatarkova
Anna
A
Drgova
Peter
P
Kaplan
Dusan
D
Dobrota
D000817:Anilino Naphthalenesulfonates / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000098:blood supply*; D042967:Electron Transport Complex I / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D006624:Hippocampus / Q000648:ultrastructure; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000502:physiology; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000817:Anilino Naphthalenesulfonates; D016159:Tumor Suppressor Protein p53; C027132:1-anilino-8-naphthalenesulfonate; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I