title: 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 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.
authors: Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's disease, University of North Texas, Health Science Center at Fort Worth, Fort Worth, TX 76107-2699, USA.Marianna.Jung@unthsc.edu
authors: Marianna E
authors: ME
authors: Jung
authors: Xiaohua
authors: X
authors: Ju
authors: Daniel B
authors: DB
authors: Metzger
authors: James W
authors: JW
authors: Simpkins
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000502:physiology*; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D055550:Protein Stability; D051381:Rats; D011916:Rats, Inbred F344; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000378:metabolism*; D013379:Substrate Specificity / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D002492:Central Nervous System Depressants; D051028:bcl-2-Associated X Protein; D000431:Ethanol; D003576:Electron Transport Complex IV