Nottet H S, van Asbeck B S, de Graaf L, de Vos N M, Visser M R, Verhoef J
Eijkman-Winkler Laboratory for Medical Microbiology, University of Utrecht, The Netherlands.
J Leukoc Biol. 1994 Dec;56(6):702-7. doi: 10.1002/jlb.56.6.702.
N-acetyl-L-cysteine (NAC) has been proposed as a therapeutic agent for AIDS patients because it reduces human immunodeficiency virus type 1 (HIV-1) replication in stimulated T cells. However, NAC and glutathione enhanced acute HIV-1 replication in monocyte-derived macrophages. Buthionine sulfoximine did not affect NAC-mediated enhanced HIV-1 replication, indicating that the NAC-mediated effects are glutathione-independent. Superoxide dismutase and the hydroxyl radical scavengers dimethylthiourea and thiourea, but not urea, inhibited acute HIV-1 replication in macrophages. NAC reduced ferricytochrome c and increased dose-dependently Fe(III)-citrate and Fe(III)-EDTA-catalyzed hydroxyl radical formation in a system using glucose and glucose oxidase. Dimethylthiourea and thiourea, but not urea and superoxide dismutase, dose-dependently inhibited NAC-mediated enhancement of HIV-1 replication. These data suggest that oxygen radicals play an important role in self-sustained HIV-1 replication in macrophages and that oxygen radical scavengers other than NAC should be considered as therapeutic agents for AIDS patients.
N-乙酰-L-半胱氨酸（NAC）已被提议作为艾滋病患者的治疗药物，因为它能减少1型人类免疫缺陷病毒（HIV-1）在受刺激T细胞中的复制。然而，NAC和谷胱甘肽会增强单核细胞衍生巨噬细胞中HIV-1的急性复制。丁硫氨酸亚砜胺并不影响NAC介导的HIV-1复制增强，这表明NAC介导的效应不依赖于谷胱甘肽。超氧化物歧化酶以及羟基自由基清除剂二甲基硫脲和硫脲（而非尿素）可抑制巨噬细胞中HIV-1的急性复制。在使用葡萄糖和葡萄糖氧化酶的体系中，NAC会使高铁细胞色素c减少，并使柠檬酸铁（III）和乙二胺四乙酸铁（III）催化的羟基自由基形成呈剂量依赖性增加。二甲基硫脲和硫脲（而非尿素和超氧化物歧化酶）呈剂量依赖性地抑制NAC介导的HIV-1复制增强。这些数据表明，氧自由基在巨噬细胞中HIV-1的自我持续复制中起重要作用，并且除NAC外的氧自由基清除剂应被视为艾滋病患者的治疗药物。
