Ethanol withdrawal posttranslationally decreases the activity of cytochrome c oxidase in an estrogen reversible manner.
Cytochrome c oxidase (COX) is a key mitochondrial enzyme that catalyzes electron transfer at the terminal stage of respiratory chain and is composed of multisubunits. We hypothesize that ethanol withdrawal (EW) impairs the activity of COX and estrogen deprivation exacerbates this problem. Five-month-old ovariectomized rats with or without 17beta-estradiol (E2) replacement received a control dextrin or a liquid ethanol diet (6.5%, 5 weeks). They were then sacrificed either during ethanol exposure or at 24h of EW (EW group). Mitochondria of the cerebellum and cortex were processed to measure the activities of total COX, COX subunit I, and IV. The effects of EW and E2 on the protein levels of these subunits were also assessed using an immunoblotting method. As compared to the control dextrin and ethanol exposure, EW decreased the activities of total COX, COX I, and COX IV. E2 treatment prevented the effects of EW on the activities of total COX and COX IV but not COX I. Neither EW nor E2 altered the protein levels of the subunits. These findings suggest that a counteracting relationship exists between the effects of EW and E2 on the activity of COX in a subunit specific manner.
Jung
Marianna E
ME
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA. mjung@hsc.unt.edu
Agarwal
Rajnee
R
Simpkins
James W
JW
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003576:Electron Transport Complex IV / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D015151:Immunoblotting; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D016133:Polymerase Chain Reaction; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D002492:Central Nervous System Depressants; D000431:Ethanol; D004958:Estradiol; D003576:Electron Transport Complex IV