Ataxia telangiectasia mutated influences cytochrome c oxidase activity.
Biochem Biophys Res Commun
; 405(4): 599-603, 2011 Feb 25.
Article
in En
| MEDLINE
| ID: mdl-21266166
ABSTRACT
Cells lacking ataxia telangiectasia mutated (ATM) have impaired mitochondrial function. Furthermore, mammalian cells lacking ATM have increased levels of reactive oxygen species (ROS) as well as mitochondrial DNA (mtDNA) deletions in the region encoding for cytochrome c oxidase (COX). We hypothesized that ATM specifically influences COX activity in skeletal muscle. COX activity was â¼40% lower in tibialis anterior from ATM-deficient mice than for wild-type mice (P < 0.01, n = 9/group). However, there were no ATM-related differences in activity of succinate dehydrogenase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, mitochondrial glycerol 3-phosphate dehydrogenase, or complex III. Incubation of wild-type extensor digitorum longus muscles for 1h with the ATM inhibitor KU55933 caused a â¼50% reduction (P<0.05, n = 5/group) in COX activity compared to muscles incubated with vehicle alone. Among the control muscles and muscles treated with the ATM inhibitor, COX activity was correlated (r = 0.61, P<0.05) with activity of glucose 6-phosphate dehydrogenase, a key determinant of antioxidant defense through production of NADPH. Overall, the findings suggest that ATM has a protective role for COX activity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Serine-Threonine Kinases
/
Electron Transport Complex IV
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Muscle, Skeletal
/
Cell Cycle Proteins
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Tumor Suppressor Proteins
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DNA-Binding Proteins
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Mitochondria, Muscle
Limits:
Animals
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2011
Type:
Article
Affiliation country:
United States