Ethanol withdrawal hastens the aging of cytochrome c oxidase

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• 作者：Marianna E. Jung ; ^{Marianna.Jung@unthsc.edu} ; Xiaohua Ju ; Daniel B. Metzger ; James W. Simpkins
• 关键词：Age ; Brain aging ; Female rats ; BAX (Bcl2-associated X protein) ; Cytochrome c ; Cytochrome c oxidase ; 17¦Â-estradiol ; Ethanol withdrawal ; Mitochondria ; Mitochondrial membrane swelling ; Mitochondrial respiration
• 刊名：Neurobiology of Aging
• 出版年：2012
• 出版时间：March 2012
• 年：2012
• 卷：33
• 期：3
• 页码：618.e21-618.e32
• 全文大小：1877 K

文摘

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 17¦Â-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.