REACTIVE OXYGEN INTERMEDIATES AS APPARENTLY WIDELY USED MESSENGERS IN THE ACTIVATION OF THE NF-KAPPA-B TRANSCRIPTION FACTOR AND HIV-1

REACTIVE OXYGEN INTERMEDIATES AS APPARENTLY WIDELY USED MESSENGERS IN THE ACTIVATION OF THE NF-KAPPA-B TRANSCRIPTION FACTOR AND HIV-1
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DOI:
10.1002/j.1460-2075.1991.tb07761.x
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发表时间:
1991-08-01
期刊:
影响因子:
11.4
通讯作者:
BAEUERLE, PA
BAEUERLE, PA
中科院分区:
生物学1区
文献类型:
--
作者:
SCHRECK, R;RIEBER, P;BAEUERLE, PA

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过氧化氢和氧自由基是炎症过程中通常产生的物质。在这项研究中,我们表明,微摩尔浓度的过氧化氢可以诱导人类T细胞系中的HIV-1的表达和复制。该作用由NF-κ-B转录因子介导,该转录因子通过H2 O2处理细胞而从其失活的细胞质形式有效且快速地活化。N-乙酰基-L-半胱氨酸(NAC)是一种充分表征的抗氧化剂,可抵消活细胞中活性氧中间体(ROI)的作用,可防止H2 O2激活NF-κ-B。NAC和其他硫醇化合物也阻断了放线菌酮、双链RNA、钙离子载体、TNF-α、活性佛波酯、白细胞介素-1、脂多糖和凝集素对NF-κ-B的激活。这表明,被认为通过不同的细胞内途径激活NF-κ B B的不同试剂可能都通过涉及ROI合成的共同机制起作用。ROI似乎充当信使,直接或间接介导抑制性亚基I-κ-B从NF-κ-B的释放。
Hydrogen peroxide and oxygen radicals are agents commonly produced during inflammatory processes. In this study, we show that micromolar concentrations of H2O2 can induce the expression and replication of HIV-1 in a human T cell line. The effect is mediated by the NF-kappa-B transcription factor which is potently and rapidly activated by an H2O2 treatment of cells from its inactive cytoplasmic form. N-acetyl-L-Cysteine (NAC), a well characterized antioxidant which counteracts the effects of reactive oxygen intermediates (ROI) in living cells, prevented the activation of NF-kappa-B by H2O2. NAC and other thiol compounds also blocked the activation of NF-kappa-B by cycloheximide, double-stranded RNA, calcium ionophore, TNF-alpha, active phorbol ester, interleukin-1, lipopolysaccharide and lectin. This suggests that diverse agents thought to activate NF-kappa-B by distinct intracellular pathways might all act through a common mechanism involving the synthesis of ROI. ROI appear to serve as messengers mediating directly or indirectly the release of the inhibitory subunit I-kappa-B from NF-kappa-B.