Thiol compounds interact with nitric oxide in regulating heme oxygenase-1 induction in endothelial cells - Involvement of superoxide and peroxynitrite anions
Thiol compounds interact with nitric oxide in regulating heme oxygenase-1 induction in endothelial cells - Involvement of superoxide and peroxynitrite anions
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DOI：
10.1074/jbc.272.29.18411
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发表时间：
1997-07-18
影响因子：
4.8
通讯作者：
Motterlini, R
中科院分区：
文献类型：
--
作者：
Foresti, R;Clark, JE;Motterlini, R
硫醇是非常重要的抗氧化剂，可以保护细胞免受氧化损伤。最近，由于这些化合物在生物系统中参与一氧化氮（NO）的结合和运输，它们被定义为一种不同的新的生理作用，鉴于这些特征，我们研究了硫醇和NO对血红素加氧酶（HO-1）诱导形式表达的影响，血红素加氧酶是一种将血红素降解为一氧化碳和胆绿素的应激蛋白。体外培养的牛主动脉内皮细胞暴露于NO供体硝普钠（SNP）和s -亚硝基-n -乙酰青霉胺（SNAP）后，血红素加氧酶活性和HO-1表达增加。与n -乙酰半胱氨酸（谷胱甘肽合成的前体）共孵育，显著减弱了SNP和SNAP对血红素加氧酶的诱导作用，并且当细胞在暴露于NO供体之前与n -乙酰半胱氨酸预孵育16小时时，也观察到血红素加氧酶活性降低。这种效应似乎与硫醇通过形成s -亚硝基硫醇来稳定NO有关。羟钴胺素，一种特异性NO清除剂，显著降低内皮血红素加氧酶活性，表明NO供体释放的NO直接参与调节应激蛋白的表达。此外，研究发现，超氧阴离子(0（-).(2)）及其与NO的反应产物过氧亚硝酸盐（ONOO-）在一定程度上促进了NO介导的内皮血红素加氧酶的激活。因此，我们认为自由NO， 0（-）之间存在动态平衡。(2)和内源性谷胱甘肽，它们可能构成了调节组织应激和适应性反应的相互作用信号机制。
Thiols are very important antioxidants that protect cells against oxidative insults. Recently, a different and new physiological role has been defined for these compounds because of their involvement in nitric oxide (NO) binding and transport in biological systems, in view of these characteristics, we examined the effect of thiols and NO on the expression of the inducible form of heme oxygenase (HO-1), a stress protein that degrades heme to carbon monoxide and biliverdin. Cultured bovine aortic endothelial cells exposed to the NO donors sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) resulted in increased heme oxygenase activity and HO-1 expression. Co-incubation with N-acetylcysteine, a precursor of glutathione synthesis, significantly attenuated heme oxygenase induction by SNP and SNAP, and a reduction in heme oxygenase activity was also observed when cells were preincubated with N-acetylcysteine for 16 h prior to exposure to NO donors. This effect appears to be associated with NO stabilization by thiols through the formation of S-nitroso-thiols. Hydroxocobalamin, a specific NO scavenger, significantly decreased endothelial heme oxygenase activity, indicating a direct involvement of NO released by NO donors to regulate the expression of this stress protein. Moreover, superoxide anion (0(-).(2)) and its reaction product with NO, peroxynitrite (ONOO-), were found to partially contribute to the observed NO-mediated activation of endothelial heme oxygenase. Thus, we suggest the existence of a dynamic equilibrium among free NO, 0(-).(2), and endogenous glutathione, which might constitute an interactive signaling mechanism modulating stress and adaptive responses in tissues.