Nitric-oxide-induced inhibition of mitochondrial complexes following aglycaemic hypoxia in neonatal cortical rat brain slices.
The effect of aglycaemic hypoxia (AH) on the activity of the mitochondrial respiratory chain complexes was measured in superfused neonatal cortical brain slices. After 30 min AH, there were no significant changes in the activities of complex I, II-III and IV or citrate synthase compared to controls. Following 30 min AH and a 30-min reperfusion period (with oxygen and glucose), the activities of complex II-III and complex IV were significantly reduced (by 25 and 17%, respectively). These reductions in enzyme activity were not abrogated by removing external calcium prior to and throughout AH, but could be reversed by the presence of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine during these periods. These data suggest that NO or an NO-derived species is involved in the decreases in mitochondrial enzyme activities observed after AH
Brooks
K J
KJ
Department of Paediatrics, The Rayne Institute, University College London Hospital Medical School, UK. Keith_J_Brooks@sbphrd.com
Hargreaves
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IP
Bates
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D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D042967:Electron Transport Complex I; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000172:deficiency / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism
D009097:Multienzyme Complexes; D009569:Nitric Oxide; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D005947:Glucose