Tobacco-smoke-inducible human haem oxygenase-1 gene expression: role of distinct transcription factors and reactive oxygen intermediates
Tobacco-smoke-inducible human haem oxygenase-1 gene expression: role of distinct transcription factors and reactive oxygen intermediates
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DOI：
10.1042/0264-6021:3530475
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发表时间：
2001-02-01
影响因子：
4.1
通讯作者：
Polla, BS
中科院分区：
文献类型：
--
作者：
Favatier, F;Polla, BS
真核细胞暴露于各种活性氧中间体（ROI）介导的细胞损伤源，包括重金属和紫外线辐射，诱导热休克（HS）和应激相关基因的表达，其中32-34 kDa蛋白被鉴定为诱导血红素加氧酶-1 （HO-1）。我们之前的研究表明，烟草烟雾（TS）是导致氧化应激的氧化剂的有效来源，在正常的人类单核细胞中诱导HS蛋白（HSPs）和HO-1。本文对HO-1启动子区[热休克因子（HSF）、核因子κ b （nf - κ b）和激活蛋白-1 (AP-I)]和镉反应元件（CdRE）的元件和结合位点进行了一致的研究，这些元件由Takeda， Ishizawa, Sate, Yoshida and Shibahara [1994] J. Biol。化学学报，26(2):558 - 567。我们报道了TS对NF-kappaB活化的抑制作用，对AP-没有影响，并且对cdr结合活性有很强的激活作用，而TS的镉螯合作用仅部分阻止了HO-1的诱导。H2O2还能激活cdr结合活性，而n -乙酰- l-半胱氨酸预处理能抑制细胞内补充GSH的水平。在ts处理的细胞中，cdr结合活性和HO-1表达均增加。
Exposure of eukaryotic cells to a variety of reactive-oxygen-intermediate (ROI)-mediated sources of cellular injury, including heavy metals and UV radiation, induces the expression of heat-shock (HS) and stress-related genes among which is a 32-34 kDa protein identified as inducible haem oxygenase-l (HO-1). We previously showed that tobacco smoke (TS), a potent source of oxidants leading to oxidative stress, induces both HS proteins (HSPs) and HO-1 in normal human monocytes. Here we with consensus elements and binding sites of the promoter region of HO-1[heat-shock factor (HSF), nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-I)] and the cadmium-responsive element (CdRE) isolated by Takeda, Ishizawa, Sate, Yoshida and Shibahara [(1994) J. Biol. Chem. 269, 22858-22867]. We report an inhibition of NF-kappaB activation by TS, no effect on AP- and a strong activation of CdRE-binding activity, whereas cadmium chelation from TS only partially prevented HO-1 induction. H2O2 also activated the CdRE-binding activity, and pretreatment with N-acetyl-L-cysteine, which replenishes the intracellular levels of GSH, suppressed. in TS-treated cells, both the CdRE-binding activity and the increased HO-1 expression.