NO/peroxynitrite dynamics of high glucose-exposed HUVECs: chemiluminescent measurement and computational model.
NO/peroxynitrite dynamics of high glucose-exposed HUVECs: chemiluminescent measurement and computational model.
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DOI：
10.1016/j.mvr.2009.04.001
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发表时间：
2009-09
影响因子：
3.1
通讯作者：
Kavdia M
中科院分区：
文献类型：
--
作者：
Potdar S;Kavdia M
许多糖尿病相关血管并发症的发病机制与内皮细胞（EC）功能障碍有关，这是EC释放的一氧化氮（NO）的生物利用度降低。NO与超氧阴离子（O2-）和过氧亚硝酸根（ONOO-）的相互作用动力学依赖于它们通过不同途径的产生和消耗。这些相互作用动力学在高葡萄糖诱导的EC功能障碍的定量知识仍然知之甚少。我们开发了一个综合的实验和计算方法，以获得定量的了解NO，O2-和ONOO-在高糖暴露的EC的相互作用。使用化学发光分析仪测量最终产物亚硝酸盐和硝酸盐。建立了一个计算生化反应网络模型，用于预测高糖对内皮细胞NO、O2-和ONOO-的影响。ECs NO和O2-生产增加，在高葡萄糖证明增加总氮氧化物浓度，主要是增加硝酸盐浓度。该模型预测在高糖条件下，O2-和ONOO-浓度增加，NO浓度降低。超氧化物歧化酶（SOD）的管理，降低O2-浓度和增加NO浓度，从而SOD改善高糖引起的这些相互作用的变化。本研究的一个重要发现是，在高糖条件下，即使EC的NO产量增加，NO的生物利用度也会下降。集成的方法提供了一个框架来预测NO，O2-和ONOO-的浓度和生产是难以测量的一个实验，将是有用的，在进一步EC功能障碍的研究。
Pathogenesis of many of diabetes-related vascular complications is associated with endothelial cell (EC) dysfunction, which is reduced bioavailability of EC-released nitric oxide (NO). Interaction dynamics of NO, superoxide (O2-) and peroxynitrite (ONOO-) are dependent on both their productions and consumptions through various pathways. Quantitative knowledge of these interaction dynamics in high glucose-induced EC dysfunction remains poorly understood. We developed an integrated experimental and computational approach to gain a quantitative understanding of the interactions of NO, O2- and ONOO- in high glucose-exposed ECs. End-products, nitrite and nitrate, were measured using a chemiluminescence analyzer. A computational biochemical reaction network model was developed to predict the effect of high glucose on ECs NO, O2- and ONOO-. ECs NO and O2- productions increased in high glucose as evidenced by increased total NOx concentration, primarily increasing nitrate concentration. The model predicted an increase in O2- and ONOO- concentrations and a decrease in NO concentration in high glucose conditions. Administration of superoxide dismutase (SOD) decreased O2- concentration and increased NO concentration, thus SOD improved high glucose-induced changes in these interactions. An important finding of this study was that the NO bioavailability decreased in high glucose conditions even though NO production of EC increased. The integrated approach provides a framework to predict NO, O2- and ONOO- concentrations and productions that are difficult to measure in one experiment and will be useful in further EC dysfunction studies.
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影响因子：
3.4
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