Staal F J, Roederer M, Raju P A, Anderson M T, Ela S W, Herzenberg L A, Herzenberg L A
Department of Genetics, Stanford University School of Medicine, California 94305.
AIDS Res Hum Retroviruses. 1993 Apr;9(4):299-306. doi: 10.1089/aid.1993.9.299.
In studies presented here, we demonstrate that antioxidants regulate NF-kappa B activation and signal transduction pathways leading to HIV expression. We show (1) that N-acetyl-L-cysteine (NAC), an antioxidant and an efficient glutathione (GSH) precursor, inhibits NF-kappa B activation and HIV expression under conditions in which GSH is depleted and NAC cannot be converted to GSH, (2) that the D-stereoisomer of NAC and a wide variety of chemically unrelated antioxidants also inhibit NF-kappa B activation and/or transcription directed by the HIV LTR, and (3) that depletion of GSH, the principal intracellular antioxidant, augments HIV production in an acute infection model. Taken together, these findings suggest direct antioxidant action as the mechanism for inhibition of HIV transcription by NAC. They also confirm that GSH, acting in its capacity as an antioxidant, regulates HIV expression and that exogenous antioxidants can potentiate this regulation.
在本文所展示的研究中，我们证明抗氧化剂可调节核因子-κB（NF-κB）的激活以及导致HIV表达的信号转导通路。我们发现：（1）N-乙酰-L-半胱氨酸（NAC）作为一种抗氧化剂及高效的谷胱甘肽（GSH）前体，在GSH耗竭且NAC无法转化为GSH的条件下，能抑制NF-κB的激活及HIV的表达；（2）NAC的D-立体异构体以及多种化学结构不相关的抗氧化剂也能抑制NF-κB的激活和/或HIV长末端重复序列（LTR）介导的转录；（3）在急性感染模型中，主要的细胞内抗氧化剂GSH的耗竭会增加HIV的产生。综合这些发现，表明直接的抗氧化作用是NAC抑制HIV转录的机制。它们还证实，GSH作为抗氧化剂发挥作用，调节HIV的表达，并且外源性抗氧化剂可以增强这种调节作用。
