کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1067585 | 948895 | 2007 | 16 صفحه PDF | دانلود رایگان |
Although alcohol drinking increases susceptibility to human immunodeficiency virus (HIV) infection, possible mechanisms underlying the effects of alcohol are not yet known. Since the HIV envelope protein gp120 plays a key role in progression of HIV infection, the aim of the present study was to evaluate the toxicity and degradation of gp120 in hepatocytes isolated from liver of alcohol-preferring rats drinking either 15% ethanol in water or pure water for 70 days. The hypothesis was that alcohol drinking augmented the toxicity, but suppressed degradation of gp120. Hepatocytes from water-drinking rats (C-cells) or ethanol-drinking rats (Et-cells) were treated with laptacystin, anti-CD4 antibodies, CCR5 antagonist, or mannose, followed by [125I]gp120 or native gp120. At predetermined intervals, control (C) and ethanol exposed (Et) cells were analyzed for toxicity and degradation of gp120. In C-cells, [125I]gp120 binding and internalization peaked within 5–45 min and remained elevated for up to 10 h and then decreased gradually. In Et-cells, [125I]gp120 binding peaked comparably to C-cells, but the binding remained to the peak level throughout the experimental period. C-cells exhibited the lysosomal/ubiquitin-mediated degradation of intracellular gp120, resulting in released gp120 fragments into the incubation medium that suppressed gp120–CD4 binding, improved cell viability, and inhibited gp120-induced apoptosis. Ethanol drinking suppressed gp120 degradation in and release of gp120 fragments from hepatocytes. The incubation medium of Et-cells did not suppress gp120–CD4 binding or the gp120-mediated apoptosis in hepatocytes. Thus, chronic alcohol drinking augmented the adverse effects of gp120 possibly by suppressing its degradation in hepatocytes. The present observation also suggests that a number of CCR5 or ubiquitin-based therapeutic drugs may not be effective in suppressing HIV infection in alcohol-drinking subjects.
Journal: Alcohol - Volume 41, Issue 8, December 2007, Pages 591–606