Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells.
Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells.
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DOI：
10.1084/jem.175.5.1181
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发表时间：
1992-05-01
影响因子：
15.3
通讯作者：
BAEUERLE, PA
中科院分区：
文献类型：
--
作者：
SCHRECK, R;MEIER, B;MANNEL, DN;DROGE, W;BAEUERLE, PA
二硫代氨基甲酸酯和铁螯合剂最近被考虑用于治疗艾滋病和神经退行性疾病。在这项研究中，我们发现二硫代氨基甲酸酯和金属螯合剂可以有效地阻断核因子κ B （nf - κ B）的激活，nf - κ B是一种转录因子，参与人类免疫缺陷病毒1型（HIV-1）在炎症过程中的表达、信号传导和早期基因激活。利用细胞培养，对二硫代氨基甲酸酯（PDTC）的吡咯烷衍生物进行了详细的研究。在用佛波酯、白细胞介素1和肿瘤坏死因子α处理的细胞中，微摩尔量的PDTC可逆地抑制NF-kappa B潜伏胞质形式的抑制亚基I κ B的释放。其他DNA结合活性和磷酯对AP-1的诱导作用不受影响。抗氧化剂PDTC还能阻断细菌脂多糖（LPS）对nf - κ B的激活，提示氧自由基在LPS的胞内信号传导中起作用。这一观点得到了支持，证明用LPS处理前B细胞和B细胞可诱导O2-和H2O2的产生。在HIV-1长末端重复序列和猿猴病毒40增强子的控制下，PDTC特异性地阻止了kappa b依赖性报告基因的转激活。本研究的结果进一步支持了氧自由基在nf - κ B和HIV-1的激活中起重要作用的观点。
Dithiocarbamates and iron chelators were recently considered for the treatment of AIDS and neurodegenerative diseases. In this study, we show that dithiocarbamates and metal chelators can potently block the activation of nuclear factor kappa B (NF-kappa B), a transcription factor involved in human immunodeficiency virus type 1 (HIV-1) expression, signaling, and immediate early gene activation during inflammatory processes. Using cell cultures, the pyrrolidine derivative of dithiocarbamate (PDTC) was investigated in detail. Micromolar amounts of PDTC reversibly suppressed the release of the inhibitory subunit I kappa B from the latent cytoplasmic form of NF-kappa B in cells treated with phorbol ester, interleukin 1, and tumor necrosis factor alpha. Other DNA binding activities and the induction of AP-1 by phorbol ester were not affected. The antioxidant PDTC also blocked the activation of NF-kappa B by bacterial lipopolysaccharide (LPS), suggesting a role of oxygen radicals in the intracellular signaling of LPS. This idea was supported by demonstrating that treatment of pre-B and B cells with LPS induced the production of O2- and H2O2. PDTC prevented specifically the kappa B-dependent transactivation of reporter genes under the control of the HIV-1 long terminal repeat and simian virus 40 enhancer. The results from this study lend further support to the idea that oxygen radicals play an important role in the activation of NF-kappa B and HIV-1.
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影响因子：
64.5
作者：
BAEUERLE, PA;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
27.4
作者：
BLAKE, DR;HALL, ND;GUTTERIDGE, JMC
通讯作者：
GUTTERIDGE, JMC
影响因子：
3.7
作者：
ENGLUND, G;HOGGAN, MD;MARTIN, MA
通讯作者：
MARTIN, MA
影响因子：
4.1
作者：
GUTTERIDGE, JMC;RICHMOND, R;HALLIWELL, B
通讯作者：
HALLIWELL, B
影响因子：
56.9
作者：
ABATE, C;PATEL, L;CURRAN, T
通讯作者：
CURRAN, T