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

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... handling is unknown. He...

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Published in:American journal of physiology: Gastrointestinal and liver physiology 2010-10, Vol.299 (4), p.G954
Main Authors: King, Adrienne L, Swain, Telisha M, Dickinson, Dale A, Lesort, Mathieu J, Bailey, Shannon M
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container_title American journal of physiology: Gastrointestinal and liver physiology
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creator King, Adrienne L
Swain, Telisha M
Dickinson, Dale A
Lesort, Mathieu J
Bailey, Shannon M
description 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... 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... accumulation. Liver mitochondria were isolated from control and ethanol-fed rats, and Ca...-mediated induction of the MPTP and mitochondrial Ca... 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... 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 was no change in the adenine nucleotide translocase and voltage-dependent anion channel. Together, these results suggest that enhanced sensitivity to Ca...-mediated MPTP induction may be due, in part, to higher Cyp D levels in liver mitochondria from ethanol-fed rats. Therefore, therapeutic strategies aimed at normalizing Cyp D levels may be beneficial in preventing ethanol-dependent mitochondrial dysfunction and liver injury. (ProQuest: ... denotes formulae/symbols omitted.)
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The mechanism responsible for increased MPTP sensitivity in ethanol-exposed mitochondria and its relation to mitochondrial Ca... 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... accumulation. Liver mitochondria were isolated from control and ethanol-fed rats, and Ca...-mediated induction of the MPTP and mitochondrial Ca... 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... retention capacity compared with control mitochondria. 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subjects Ethanol
Gene expression
Liver
Mitochondria
Oxidative stress
Permeability
Proteins
Rodents
title Chronic ethanol consumption enhances sensitivity to Ca^sup 2+^-mediated opening of the mitochondrial permeability transition pore and increases cyclophilin D in liver
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