Glutathione deficiency is associated with impaired survival in HIV disease
Glutathione deficiency is associated with impaired survival in HIV disease
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DOI：
10.1073/pnas.94.5.1967
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发表时间：
1997-03-04
影响因子：
11.1
通讯作者：
Herzenberg, LA
中科院分区：
文献类型：
--
作者：
Herzenberg, LA;DeRosa, SC;Herzenberg, LA
谷胱甘肽（GSH）是一种含半胱氨酸的三肽，对几乎所有细胞的生存力和功能都是必不可少的。体外研究表明，低GSH水平既促进HIV表达又损害T细胞功能，表明GSH耗竭与HIV疾病进展之间存在联系。这里提出的临床研究直接表明，低GSH水平预测否则难以区分的HIV感染受试者的生存率差。我们发现，这些受试者的CD 4 T细胞中GSH缺乏与基线数据收集后2-3年生存率显著降低相关（Kaplan-Meier和逻辑回归分析，两种分析P < 0.0001），这一发现，有证据表明，口服GSH前药N-乙酰半胱氨酸可使这些受试者的GSH减少，并表明N-乙酰半胱氨酸可使GSH减少。乙酰半胱氨酸给药可以改善其存活率，确定GSH缺乏是HIV疾病存活率的关键决定因素。此外，它强烈认为HIV感染者应避免不必要或过度使用对乙酰氨基酚、酒精或其他已知会消耗GSH的药物。
Glutathione (GSH), a cysteine-containing tripeptide, is essential for the viability and function of virtually all cells, In vitro studies showing that low GSH levels both promote HIV expression and impair T cell function suggested a link between GSH depletion and HIV disease progression, Clinical studies presented here directly demonstrate that low GSH levels predict poor survival in otherwise indistinguishable HIV-infected subjects, Specifically, we show that GSH deficiency in CD4 T cells from such subjects is associated with markedly decreased survival 2-3 years after baseline data collection (Kaplan-Meier and logistic regression analyses, P < 0.0001 for both analyses), This finding, supported by evidence demonstrating that oral administration of the GSH prodrug N-acetylcysteine replenishes GSH in these subjects and suggesting that N-acetylcysteine administration can improve their survival, establishes GSH deficiency as a key determinant of survival in HIV disease, Further, it argues strongly that the unnecessary or excessive use of acetaminophen, alcohol, or other drugs known to deplete GSH should be avoided by HIV-infected individuals.