Ischemia-reperfusion induces inhibition of mitochondrial protein synthesis and cytochrome c oxidase activity in rat hippocampus.
Dysfunction of mitochondria induced by ischemia is considered to be a key event triggering neuronal cell death after brain ischemia. Here we report the effect of ischemia-reperfusion on mitochondrial protein synthesis and activity of cytochrome c oxidase (EC 1.9.3.1, COX). By performing 4-vessel occlusion model of global brain ischemia, we have observed that 15 min of global ischemia led to the inhibition of COX subunit I (COXI) synthesis to 56 % of control. After 1, 3 and 24 h of reperfusion, COXI synthesis was inhibited to 46, 50 and 72 % of control, respectively. Depressed synthesis of COXI was not a result of either diminished transcription of COXI gene or increased proteolytic degradation of COXI, since both Northern hybridization and Western blotting did not show significant changes in COXI mRNA and protein level. Thus, ischemia-reperfusion affects directly mitochondrial translation machinery. In addition, ischemia in duration of 15 min and consequent 1, 3 and 24 h of reperfusion led to the inhibition of COX activity to 90.3, 80.3, 81.9 and 83.5 % of control, respectively. Based on our data, we suggest that inhibition of COX activity is rather caused by ischemia-induced modification of COX polypeptides than by inhibition of mitochondrial translation.
Racay
P
P
Institute of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic. racay@jfmed.uniba.sk
Tatarková
Z
Z
Drgová
A
A
Kaplan
P
P
Dobrota
D
D
D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D003576:Electron Transport Complex IV / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology* / Q000209:etiology; D013997:Time Factors; D014158:Transcription, Genetic
D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D003576:Electron Transport Complex IV