Transport of reduced glutathione in hepatic mitochondria and mitoplasts from ethanol-treated rats: Effect of membrane physical properties and S-adenosyl-L-methionine
✍ Scribed by A Colell; C Garcia-Ruiz; A Morales; A Ballesta; M Ookhtens; J Rodes; N Kaplowitz; J C Fernandez-Checa
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 391 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
ethanol were confined to the inner membrane; mitoplasts Ethanol intake depletes the mitochondrial pool of reduced from ethanol-fed rats showed features similar to those of intact glutathione (GSH) by impairing the transport of GSH from mitochondria such as impaired transport of GSH and incytosol into mitochondria. S-Adenosyl-L-methionine (SAM) creased order parameter. A different mitochondrial transsupplementation of ethanol-fed rats restores the mitochonporter, adenosine diphosphate (ADP)/ATP translocator, was drial pool of GSH. The purpose of the current study was to unaffected by ethanol feeding. Futhermore, fluidization of midetermine the effect of ethanol feeding on the kinetic parametochondria or mitoplasts from ethanol-fed rats by treatment ters of mitochondrial GSH transport, the fluidity of mitochonwith a fatty acid derivative restored their ability to transport dria, and the effect of SAM on these changes. Male Sprague-GSH to control levels. Thus, ethanol-induced impaired trans-Dawley rats were fed ethanol-liquid diet for 4 weeks port of GSH into mitochondria is selective, mediated by desupplemented with either SAM or N-acetylcysteine (NAC).
creased fluidity of the mitochondrial inner membrane, and SAM-supplementation of ethanol-fed rats restored the mitoprevented by SAM treatment. (HEPATOLOGY 1997;26:699chondrial GSH pool but NAC administration did not. Kinetic 708.) studies of GSH transport in isolated mitochondria revealed two saturable, adenosine triphosphate (ATP)-stimulated components that were affected significantly by chronic ethanol
The pathogenesis of the alcohol-induced liver disease is feeding: lowering V max (0.22 and 1.6 in ethanol case vs. 0.44 not completely understood, despite intense research. Multiand 2.7 nmol/15 sec/mg protein in controls) for both low and ple factors have been implicated in the pathogenesis of the high affinity components with the latter showing an increased disease. [1][2][3][4] As a consequence of ethanol metabolism there are K m (15.5 vs. 8.9, mmol/L in ethanol vs. control). Mitochondria important biochemical changes in the hepatocyte, including from SAM-supplemented ethanol-fed rats showed kinetic feacellular redox potential shift (a-nicotinamide adenine dinutures of GSH transport similar to control mitochondria. Detercleotide/a-dihydronicotinamide adenine dinucleotide demination of membrane fluidity revealed an increased order crease) and acetaldehyde production, a potent toxic intermeparameter in ethanol compared with control mitochondria, diate, which may mediate many of the toxic effects of ethanol. which was restricted to the polar head groups of the bilayer
In addition, other factors such as auto-immune-induced inand was prevented by SAM but not NAC supplementation jury by antibodies to protein-acetaldehyde adducts, hemodyof ethanol-fed rats. The changes elicited in mitochondria by namic alterations of the hepatic blood supply along sinusoids, peroxidation of membrane lipids, and oxidative stress may contribute to the development of the disease. [5][6][7] It is well Abbreviations: ATP, adenosine triphosphate; GSH, reduced glutathione; SAM, Sadenosyl-L-methionine; A2C, 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl) documented that oxidative metabolism of alcohol induces octanoate; DPH, 1,6-diphenyl-1, 3,5-hexatriene; 16-AP, 16-(9-anthroyloxy) palmitic important morphological and functional alterations in mitoacid; NAC, N-acetylcysteine; ADP, adenosine diphosphate; EDTA, ethylenediaminetetchondria resulting in lower adenosine triphosphate (ATP) raacetic acid; BSA, bovine serum albumin; PC, L-a-phosphatidylcholine; PE, L-a-phoslevels observed in chronic ethanol-fed animals. [8][9][10][11] phatidylethanolamine.