Sen C K, Traber K E, Packer L
Department of Molecular & Cell Biology, University of California-Berkeley 94720-3200, USA.
Biochem Biophys Res Commun. 1996 Jan 5;218(1):148-53. doi: 10.1006/bbrc.1996.0026.
Nuclear factor (NF)-kappa B is a redox sensitive cytosolic transcription factor. Redox regulation of NF-kappa B has been implicated in the activation of the human immuno-deficiency virus (HIV). Therefore, inhibition of NF-kappa B activation may be an effective strategy for acquired immunodeficiency syndrome therapy. Anetholdithiolthione (ADT, 5-[p-methoxyphenyl]-3H-1,2-dithiol-3-thione) is an antioxidant which has been used to protect against acetaminophen- and CCl4-induced hepatotoxicity, lipid peroxidation, radiation injury, and also has been used clinically as an anti-choleretic agent. The present study examined the effect of ADT pretreatment on NF-kappa B activation in response to a variety of stimuli such as H2O2, phorbol myristate acetate (PMA) or tumor necrosis factor alpha (TNF alpha). PMA and TNF alpha induced activation of (NF)-kappa B in human Jurkat T-cells was partially inhibited by ADT (0.1 mM) pretreatment. ADT (0.1 mM) also inhibited H2O2 induced activation of the transcription factor in the peroxide sensitive human Wurzburg T-cells. Furthermore, ADT treated Wurzburg cells had significantly higher glutathione levels as compared with untreated cells. H2O2 induced lipid peroxidation in Wurzburg cells was remarkably inhibited by ADT pretreatment. ADT, a pro-glutathione antioxidant, was observed to be capable of modulating NF-kappa B activation.
核因子（NF）-κB是一种对氧化还原敏感的胞质转录因子。NF-κB的氧化还原调节与人类免疫缺陷病毒（HIV）的激活有关。因此，抑制NF-κB激活可能是获得性免疫缺陷综合征治疗的有效策略。茴香脑二硫硫酮（ADT，5-[对甲氧基苯基]-3H-1,2-二硫醇-3-硫酮）是一种抗氧化剂，已被用于预防对乙酰氨基酚和四氯化碳诱导的肝毒性、脂质过氧化、辐射损伤，并且在临床上也被用作利胆剂。本研究检测了ADT预处理对响应多种刺激（如过氧化氢、佛波酯肉豆蔻酸酯（PMA）或肿瘤坏死因子α（TNFα））时NF-κB激活的影响。ADT（0.1 mM）预处理可部分抑制PMA和TNFα诱导的人Jurkat T细胞中（NF）-κB的激活。ADT（0.1 mM）也抑制了过氧化氢诱导的对过氧化物敏感的人维尔茨堡T细胞中转录因子的激活。此外，与未处理的细胞相比，ADT处理的维尔茨堡细胞的谷胱甘肽水平显著更高。ADT预处理可显著抑制过氧化氢诱导的维尔茨堡细胞中的脂质过氧化。ADT是一种促谷胱甘肽抗氧化剂，被观察到能够调节NF-κB的激活。
