Differential regulation of metabolism by nitric oxide and S-nitrosothiols in endothelial cells
Differential regulation of metabolism by nitric oxide and S-nitrosothiols in endothelial cells
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DOI：
10.1152/ajpheart.00210.2011
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发表时间：
2011-09-01
影响因子：
4.8
通讯作者：
Hogg, Neil
中科院分区：
文献类型：
--
作者：
Diers, Anne R.;Broniowska, Katarzyna A.;Hogg, Neil
张晓华，李晓波，等.血管内皮细胞代谢的差异调控.北京：中国人民大学出版社，2002，19(2)：343-643.Am J Physiol心圈Physiol 301：H803-H812,2011。2011年6月17日首次发表；细胞信号通路中关键蛋白质中硫醇的doi:10.1152/ajpheart.00210.2011.-S-nitrosation被认为是一氧化氮(NO)依赖的血管(病理)生理控制的重要贡献者。多种代谢酶是NO和S亚硝化的靶标，包括那些参与糖酵解和氧化磷酸化的代谢酶。因此，重要的是要了解这些代谢途径是如何通过NO依赖机制整合在一起的。在这里，我们使用细胞外通量技术比较了NO和S亚硝化对牛主动脉内皮细胞糖酵解和氧化磷酸化的影响，以确定共同和独特的调节点。化合物S-亚硝基-L-半胱氨酸(L-CysNO)被转运到细胞内，在体外可以稳定地进行S亚硝化，因此被用来引发细胞内的S亚硝化。将其作用与NO供体DetaNONOate(DetaNO)进行比较。DetaNO处理只引起储备呼吸量的下降，而L-CysNO以浓度依赖的方式损害储备呼吸量和基础呼吸。此外，DetaNO可刺激糖酵解的替代标志物胞外酸化率，而L-CysNO在低浓度时刺激胞外酸化率，而在高浓度时抑制胞外酸化率。此外，还发现了NO和S亚硝化对代谢的影响之间的时间关系，即NO引起线粒体功能的快速损害，最终被S亚硝化依赖的过程所压倒。综上所述，这些结果表明，严重的药理性亚硝化应激可能通过细胞内S亚硝化和NO依赖两种机制对代谢途径进行不同的调节。此外，这些数据还为NO及其相关化合物在血管(病理)生理学中的作用提供了洞察力。
Diers AR, Broniowska KA, Darley-Usmar VM, Hogg N. Differential regulation of metabolism by nitric oxide and S-nitrosothiols in endothelial cells. Am J Physiol Heart Circ Physiol 301: H803-H812, 2011. First published June 17, 2011; doi:10.1152/ajpheart.00210.2011.-S-nitrosation of thiols in key proteins in cell signaling pathways is thought to be an important contributor to nitric oxide (NO)-dependent control of vascular (patho)physiology. Multiple metabolic enzymes are targets of both NO and S-nitrosation, including those involved in glycolysis and oxidative phosphorylation. Thus it is important to understand how these metabolic pathways are integrated by NO-dependent mechanisms. Here, we compared the effects of NO and S-nitrosation on both glycolysis and oxidative phosphorylation in bovine aortic endothelial cells using extracellular flux technology to determine common and unique points of regulation. The compound S-nitroso-L-cysteine (L-CysNO) was used to initiate intracellular S-nitrosation since it is transported into cells and results in stable S-nitrosation in vitro. Its effects were compared with the NO donor DetaNONOate (DetaNO). DetaNO treatment caused only a decrease in the reserve respiratory capacity; however, L-CysNO impaired both this parameter and basal respiration in a concentration-dependent manner. In addition, DetaNO stimulated extracellular acidification rate (ECAR), a surrogate marker of glycolysis, whereas L-CysNO stimulated ECAR at low concentrations and inhibited it at higher concentrations. Moreover, a temporal relationship between NO-and S-nitrosation-mediated effects on metabolism was identified, whereby NO caused a rapid impairment in mitochondrial function, which was eventually overwhelmed by S-nitrosation-dependent processes. Taken together, these results suggest that severe pharmacological nitrosative stress may differentially regulate metabolic pathways through both intracellular S-nitrosation and NO-dependent mechanisms. Moreover, these data provide insight into the role of NO and related compounds in vascular (patho)physiology.