Chronic ethanol consumption enhances sensitivity to Ca(2+)-mediated opening of the mitochondrial permeability transition pore and increases cyclophilin D in liver.

American Journal of Physiology. Gastrointestinal and Liver Physiology
Adrienne L KingShannon M Bailey

Abstract

Chronic ethanol consumption increases mitochondrial oxidative stress and sensitivity to form the mitochondrial permeability transition pore (MPTP). The mechanism responsible for increased MPTP sensitivity in ethanol-exposed mitochondria and its relation to mitochondrial Ca(2+) handling is unknown. Herein, we investigated whether increased sensitivity to MPTP induction in liver mitochondria from ethanol-fed rats compared with controls is related to an ethanol-dependent change in mitochondrial Ca(2+) accumulation. Liver mitochondria were isolated from control and ethanol-fed rats, and Ca(2+)-mediated induction of the MPTP and mitochondrial Ca(2+) retention capacity were measured. Levels of proposed MPTP proteins as well as select pro- and antiapoptotic proteins were measured along with gene expression. We observed increased steatosis and TUNEL-stained nuclei in liver of ethanol-fed rats compared with controls. Liver mitochondria from ethanol-fed rats had increased levels of proapoptotic Bax protein and reduced Ca(2+) retention capacity compared with control mitochondria. We observed increased cyclophilin D (Cyp D) gene expression in liver and protein in mitochondria from ethanol-fed animals compared with controls, whereas there w...Continue Reading

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Citations

Apr 25, 2012·Pflügers Archiv : European journal of physiology·Sudipto DasGyörgy Hajnóczky
Jul 30, 2011·Biomedical Microdevices·Samantha M HattersleyStephen John Haswell
Dec 21, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Adrienne L KingShannon M Bailey
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Oct 25, 2014·Current Pathobiology Reports·Carmen García-RuizJosé C Fernandez-Checa
Mar 23, 2021·FEBS Letters·Chaonan JinJean-François Dufour
Aug 12, 2021·Therapeutic Advances in Gastroenterology·Paul Middleton, Nikhil Vergis
Dec 30, 2014·Redox Biology·Whitney S TheisShannon M Bailey

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