Ethanol withdrawal hastens the aging of cytochrome c oxidase

Abstract We investigated whether abrupt ethanol withdrawal (EW) age-specifically inhibits a key mitochondrial enzyme, cytochrome c oxidase (COX), and whether estrogen mitigates this problem. We also tested whether this possible effect of EW involves a substrate (cytochrome c) deficiency that is asso...

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Bibliographic Details
Published in:Neurobiology of aging 2012-03, Vol.33 (3), p.618.e21-618.e32
Main Authors: Jung, Marianna E, Ju, Xiaohua, Metzger, Daniel B, Simpkins, James W
Format: Article
Language:English
Subjects:
17β-estradiol
Age
Aging - drug effects
Aging - metabolism
Animals
BAX (Bcl2-associated X protein)
bcl-2-Associated X Protein - metabolism
Brain aging
Central Nervous System Depressants - adverse effects
Cytochrome c
Cytochrome c oxidase
Electron Transport Complex IV - chemistry
Electron Transport Complex IV - physiology
Ethanol - adverse effects
Ethanol withdrawal
Female
Female rats
Internal Medicine
Mitochondria
Mitochondrial membrane swelling
Mitochondrial respiration
Neurology
Protein Stability
Rats
Rats, Inbred F344
Substance Withdrawal Syndrome - etiology
Substance Withdrawal Syndrome - metabolism
Substrate Specificity - genetics
Up-Regulation - genetics
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Summary:Abstract We investigated whether abrupt ethanol withdrawal (EW) age-specifically inhibits a key mitochondrial enzyme, cytochrome c oxidase (COX), and whether estrogen mitigates this problem. We also tested whether this possible effect of EW involves a substrate (cytochrome c) deficiency that is associated with proapoptotic Bcl2-associated X protein (BAX) and mitochondrial membrane swelling. Ovariectomized young, middle age, and older rats, with or without 17β-estradiol (E2) implantation, underwent repeated EW. Cerebelli were collected to measure COX activity and the mitochondrial membrane swelling using spectrophotometry and the mitochondrial levels of cytochrome c and BAX using an immunoblot method. The loss of COX activity and the mitochondrial membrane swelling occurred only in older rats under control diet conditions but occurred earlier, starting in the young rats under EW conditions. E2 treatment mitigated these EW effects. EW increased mitochondrial BAX particularly in middle age rats but did not alter cytochrome c. Collectively EW hastens but E2 delays the age-associated loss of COX activity. This EW effect is independent of cytochrome c but may involve the mitochondrial overload of BAX and membrane vulnerability.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2011.02.002