Zinc regulates iNOS-derived nitric oxide formation in endothelial cells.
Zinc regulates iNOS-derived nitric oxide formation in endothelial cells.
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DOI：
10.1016/j.redox.2014.06.011
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发表时间：
2014
期刊：
影响因子：
11.4
通讯作者：
Suschek, Christoph V.
中科院分区：
文献类型：
--
作者：
Cortese-Krott, Miriam M.;Kulakov, Larissa;Oplaender, Christian;Kolb-Bachofen, Victoria;Kroencke, Klaus-D.;Suschek, Christoph V.
诱导型一氧化氮合酶(INOS)引起的一氧化氮(NO)的异常产生与内皮功能障碍和血管疾病的发生密切相关。炎症中iNOS活性微调的机制仍不完全清楚。锌是一氧化氮合酶的重要结构元素，对其催化活性有抑制作用。本研究旨在探讨锌对血管内皮细胞诱导型一氧化氮合酶活性和表达的影响。我们发现锌下调了iNOS(mRNA+蛋白)的表达，并减少了细胞因子介导的iNOS启动子的激活。锌对诱导型一氧化氮合酶表达的调节是由于抑制了核因子-κB的反式激活活性，这是由于抑制了核因子-κB驱动的荧光素酶报告活性和包括环氧合酶2和IL-1β在内的核因子-核糖核酸酶B靶基因的表达。然而，通过核和胞浆部分的Western印迹分析，锌并不影响NF-κB移位到核中。综上所述，我们的结果表明，锌通过抑制NF-κB依赖的诱导型一氧化氮合酶的表达，限制了诱导型一氧化氮合酶在内皮细胞中的高产量产生，表明锌在炎症中作为诱导型一氧化氮合酶活性的调节因子。锌抑制内皮细胞内iNOS依赖的亚硝酸盐积聚。锌降低细胞因子诱导的内皮细胞iNOS表达。锌抑制iNOS启动子活性。核因子-kB沉默可消除细胞因子诱导的iNOS表达。锌抑制核因子-κB的反式激活活性。
Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation. Zinc inhibits iNOS-dependent nitrite accumulation in endothelial cells. Zinc decreases cytokine-induced iNOS expression in endothelial cells. Zinc inhibits iNOS promoter activity. NF-kB silencing abolishes cytokine-induced iNOS expression. Zinc inhibits the transactivation activity of NF-κB.
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影响因子：
5.5
作者：
Cortese-Krott, Miriam M.;Suschek, Christoph V.;Kolb-Bachofen, Victoria
通讯作者：
Kolb-Bachofen, Victoria
影响因子：
4.8
作者：
Gazaryan, IG;Krasnikov, BF;Brown, AM
通讯作者：
Brown, AM
影响因子：
4.4
作者：
Jeon, KI;Jeong, JY;Jue, DM
通讯作者：
Jue, DM
DOI：
10.1006/bbrc.1994.1564
发表时间：
1994-04-29
影响因子：
3.1
作者：
KRONCKE, KD;FEHSEL, K;KOLBBACHOFEN, V
通讯作者：
KOLBBACHOFEN, V
DOI：
10.1080/07315724.1999.10718843
发表时间：
1999-04-01
影响因子：
3.5
作者：
Hennig, B;Meerarani, P;McClain, CJ
通讯作者：
McClain, CJ