Aminothiols protect endothelial cell proliferation against inhibition by lipopolysaccharide.
Aminothiols protect endothelial cell proliferation against inhibition by lipopolysaccharide.
复制标题
氨基硫醇保护内皮细胞增殖免受脂多糖的抑制。
DOI：
10.1097/00024382-199812000-00008
复制
发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Rubin,DB
中科院分区：
文献类型：
--
作者：
Drab-Weiss,EA;Hansra,IK;Blazek,ER;Rubin,DB
脂多糖(LPS)是脓毒症的主要致病因子，可损伤血管内皮。内皮细胞增殖是修复受损内皮细胞的关键，对抗内毒素对内皮细胞增殖的抗增殖作用的药物应该是有益的。由于内毒素的大部分细胞毒性作用是通过产生活性氧和氮中间产物来实现的，因此了解治疗性抗氧化剂硫醇是否能维持受损内皮细胞的增殖将是很有帮助的。本研究发现，内毒素可通过诱导细胞凋亡和减少DNA合成来抑制牛主动脉内皮细胞的增殖。由于其对辐射内皮细胞的好处，我们随后用放射和化学保护的氨基硫醇WR-1065([N-2-甲硫乙基]-1-3-二氨基丙烷，氨磷汀(R)/乙醇(R)的活性形式)处理这些细胞。WR-1065可减轻脂多糖对DNA合成的抑制作用。WR-33278的二硫键具有促进脱氧核糖核酸合成和抑制细胞凋亡的作用。二硫化物的有效性表明，细胞毒性的降低并不一定是清除自由基的结果。这些发现表明，氨基硫醇在促进内毒素损伤的内皮细胞DNA合成和降低细胞凋亡方面具有新的作用。
Lipopolysaccharide (LPS) is a primary agent of sepsis that damages the vascular endothelium. Endothelial cell proliferation is key to the repair of damaged endothelium, and drugs that counteract the antiproliferative impact of LPS on endothelial cells should be beneficial. Because LPS exerts much of its cytotoxicity by generating reactive oxygen and nitrogen intermediates, it would be helpful to know whether therapeutic antioxidant thiols maintain cell proliferation in injured endothelium. In this study, it was found that LPS inhibited bovine aortic endothelial cell proliferation by inducing apoptosis and by decreasing DNA synthesis. Because of its benefit to irradiated endothelial cells, we then treated the cells with a radio and chemoprotective aminothiol, WR-1065 ([N-2-mecaptoethyl]-1-3-diaminopropane, the active form of Amifostine (R)/Ethyol (R)). WR-1065 attenuated the inhibition of DNA synthesis caused by LPS exposure. The disulfide of WR-1065, WR-33278, was tested and shown to both promote DNA synthesis and inhibit apoptosis. The effectiveness of the disulfide suggests that the reduction of cytotoxicity does not necessarily result from the scavenging of free radicals. These findings demonstrate a novel role for aminothiols in promoting DNA synthesis and lowering apoptosis in endothelium injured with LPS.