Nitric oxide and peroxynitrite released by ultraviolet B-irradiated human endothelial cells are possibly involved in skin erythema and inflammation
Nitric oxide and peroxynitrite released by ultraviolet B-irradiated human endothelial cells are possibly involved in skin erythema and inflammation
复制标题
DOI：
10.1113/expphysiol.1996.sp003986
复制
发表时间：
1996-11-01
影响因子：
2.7
通讯作者：
Stavrides, JC
中科院分区：
文献类型：
--
作者：
Deliconstantinos, G;Villiotou, V;Stavrides, JC
在这项研究中，我们试图证明是否内皮细胞一氧化氮合酶（eNOS）和黄嘌呤氧化酶（XO）可以被激活，释放一氧化氮（NO）和过氧亚硝酸盐（ONOO-）暴露于紫外线B（UVB）辐射后，并确定这种光诱导的反应是否可以参与晒伤红斑和炎症的发病机制。用UVB（290-320 nm）辐射（高达100 mJ/cm（2））处理人内皮细胞导致NO和ONOO-释放增加，而N-G-单甲基-L-精氨酸（L-NMMA）可抑制NO和ONOO-释放。用各种剂量的UVB辐射（高达20 mJ/cm 2）处理细胞胞质溶胶导致XO活性增加三倍，而XO活性被oxypurinol抑制（约90%）。在重建实验中，当纯化的eNOS加入到纯化的XO中时，观察到在20 mJ/cm（2）UVB辐射下ONOO产量增加了近四倍。UVB辐射（100 mJ/cm（2））降低细胞膜流动性，表明膜的物理化学特性的变化。在体内实验中，当人类志愿者经受UVB光时，当将含有硝基-L-精氨酸（L-NA; 2%）和L-NMMA（2%）的乳化乳膏制剂施用到他们的皮肤上时，计算出保护因子（PF）为3.90 +/- 0.85。目前的研究表明，UVB辐射作为一个有效的刺激人内皮细胞中的eNOS和XO。NO和ONOO-的细胞毒性作用可能是导致血管舒张的皮肤综合反应中的主要因素，血管舒张是红斑产生和炎症过程的第一个关键事件。
In this study we attempted to demonstrate whether endothelial cell nitric oxide synthase (eNOS) and xanthine oxidase (XO) could be activated to release nitric oxide (NO) and peroxynitrite (ONOO-) following exposure to ultraviolet B (UVB) radiation and to define whether this light-induced response could be involved in the pathogenesis of sunburn erythema and inflammation. Treatment of human endothelial cells with UVB (290-320 nm) radiation (up to 100 mJ/cm(2)) resulted in an increase of both NO and ONOO- release that was inhibited by N-G-monomethyl-L-arginine (L-NMMA). Treatment of cell cytosol with various doses of UVB radiation (up to 20 mJ/cm2) resulted in a threefold increase of XO activity that was inhibited (approximately 90 %) by oxypurinol. In reconstitution experiments, when purified eNOS was added to purified XO, an almost fourfold increase in ONOO production at 20 mJ/cm(2) UVB radiation was observed. UVB radiation (100 mJ/cm(2)) decreased cell membrane fluidity, indicating changes in the physico-chemical characteristics of the membranes. In in vivo experiments, when human volunteers were subjected to UVB light, a protection factor (PF) of 3.90 +/- 0.85 was calculated when an emulsified cream formulation containing nitro-L-arginine (L-NA; 2 %) and L-NMMA (2 %) was applied to their skin. The present studies indicate that UVB radiation acts as a potent stimulator of eNOS and XO in human endothelial cells. The cytotoxic effects of NO and ONOO- may be the main factors in the integrated response of the skin leading to vasodilatation, the first key event of erythema production and the inflammation process.