一氧化氮通过抑制核因子κB与DNA的结合来调节一氧化氮合酶-2基因的表达。
Nitric oxide regulates nitric oxide synthase-2 gene expression by inhibiting NF-kappaB binding to DNA.
作者信息
Park S K, Lin H L, Murphy S
机构信息
Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242, U.S.A.
出版信息
Biochem J. 1997 Mar 1;322 ( Pt 2)(Pt 2):609-13. doi: 10.1042/bj3220609.
Abstract
Treatment of astroglial cells with interleukin 1beta and interferon gamma transcriptionally activates the nitric oxide synthase (NOS)-2 gene. The duration of mRNA expression is brief because of transcript instability. In addition, NO donors reduce the expression of NOS-2 mRNA dramatically by reducing the rate of transcription. In this study we observed that the NO donor, spermine NONOate did not inhibit the activation and translocation of NF-kappaB, a key transcription factor in the induction of NOS-2, but inhibited formation of the NF-kappaB-DNA complex. This effect was reversed by methaemoglobin (acting as an NO trap) and by the reducing agent dithiothreitol. Formation of the interferon-regulatory factor-DNA complex was unaffected by NO. These results suggest that NO can modulate its own production by interfering with NF-kappaB interaction with the promoter region of the NOS gene, a negative feedback effect that may be important for limiting NO production in vivo.
摘要
用白细胞介素1β和干扰素γ处理星形胶质细胞可转录激活一氧化氮合酶（NOS）-2基因。由于转录本不稳定，mRNA表达的持续时间较短。此外，NO供体通过降低转录速率显著降低NOS-2 mRNA的表达。在本研究中，我们观察到NO供体亚精胺NONOate并不抑制NF-κB的激活和易位，NF-κB是诱导NOS-2的关键转录因子，但可抑制NF-κB-DNA复合物的形成。高铁血红蛋白（作为NO捕获剂）和还原剂二硫苏糖醇可逆转这种效应。干扰素调节因子-DNA复合物的形成不受NO的影响。这些结果表明，NO可通过干扰NF-κB与NOS基因启动子区域的相互作用来调节其自身的产生，这种负反馈效应可能对限制体内NO的产生很重要。
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