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Title: Impaired uptake of glutathione by hepatic mitochondria from chronic ethanol-fed rats. Tracer kinetic studies in vitro and in vivo and susceptibility to oxidant stress.
Author: Fernández-Checa Torres, José Carlos
García Ruiz, Carmen
Ookhtens, Murad
Kaplowitz, Neil
Keywords: Glutatió
Malalties del fetge
Rates (Animals de laboratori)
Investigació mèdica
Ethanol toxicity
Glutathione metabolism
Liver mitochondria
Issue Date: 1991
Publisher: American Society for Clinical Investigation
Abstract: Isolated hepatocytes incubated with [35S]-methionine were examined for the time-dependent accumulation of [35S]-glutathione (GSH) in cytosol and mitochondria, the latter confirmed by density gradient purification. In GSH-depleted and -repleted hepatocytes, the increase of specific activity of mitochondrial GSH lagged behind cytosol, reaching nearly the same specific activity by 1-2 h. However, in hepatocytes from ethanol-fed rats, the rate of increase of total GSH specific radioactivity in mitochondria was markedly suppressed. In in vivo steady-state experiments, the mass transport of GSH from cytosol to mitochondria and vice versa was 18 nmol/min per g liver, indicating that the half-life of mitochondrial GSH was approximately 18 min in controls. The fractional transport rate of GSH from cytosol to mitochondria, but not mitochondria to cytosol, was significantly reduced in the livers of ethanol-fed rats. Thus, ethanol-fed rats exhibit a decreased mitochondrial GSH pool size due to an impaired entry of cytosol GSH into mitochondria. Hepatocytes from ethanol-fed rats exhibited a greater susceptibility to the oxidant stress-induced cell death from tert-butylhydroperoxide. Incubation with glutathione monoethyl ester normalized the mitochondrial GSH and protected against the increased susceptibility to t-butylhydroperoxide, which was directly related to the lowered mitochondrial GSH pool size in ethanol-fed cells.
Note: Reproducció del document publicat a
It is part of: Journal of Clinical Investigation, 1991, vol. 87, núm. 2, p. 397-405
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ISSN: 0021-9738
Appears in Collections:Articles publicats en revistes (Medicina)

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