| Title | Polyaspartoyl L-arginine protects endothelial cells against injury |
| Authors | Jian, Yang Tang, Zhiyu Wang, Yinye Peng, Shiqi |
| Affiliation | Peking Univ, Sch Pharmaceut Sci, Dept Mol & Cellular Pharmacol, Beijing 100083, Peoples R China. Capital Univ Med Sci, Beijing Key Labs Hydrone & Peptides, Beijing 100069, Peoples R China. |
| Keywords | Polyaspartoyl L-arginine Rat aorta endothelial cell Oxidative injury Apoptosis L-arginine Nitric oxide NITRIC-OXIDE APOPTOSIS PROSTACYCLIN STIMULATION MACROPHAGES THROMBOSIS DEATH |
| Issue Date | 2008 |
| Publisher | european journal of pharmacology |
| Citation | EUROPEAN JOURNAL OF PHARMACOLOGY.2008,599,(1-3),96-101. |
| Abstract | Polyaspartoyl L-arginine (PDR) is an anti-thrombotic agent and its anti-thrombotic effect is related with endothelial cells. This study is to investigate the effect of PDR on the endothelial cells. In cell injury assay 1.7-170 mu g/ml of PDR significantly increased the viability of rat aorta endothelial cells (RAECs) injured by H(2)O(2), this effect was comparable with that of 95 mu g/ml of alpha-tocopherol, and was more powerful than that of L-arginine. Nitric oxide synthase(NOS) inhibitor, L-NAME, almost abolished the effect of PDR, but not influence the effect of alpha-tocopherol or L-arginine. PDR enhanced the viability of RAECs injured by oxidized-low density lipoprotein (ox-LDL) either, which was comparable to that of alpha-tocopherol, whereas L-arginine, L-aspartic acid alone or their combined use failed to showed effects. PDR (17-170 mu g/ml) raised nitrite level in RAEC medium, which is the major end-product of NO, but L-arginine (170 mu g/ml) produced insignificant nitrite level rise. In addition, in the absence of RAEC PDR and L-arginine but alpha-tocopherol failed to lower the concentration of oxidative product (Fe(3+)) in a cell free system, whereas in the presence of RAEC PDR L-arginine or alpha-tocopherol all significantly reduced the concentration of Fe(3+). In cell apoptosis assay PDR (17-170 mu g/ml) lowered the percentage of early apoptotic and late apoptotic RAECs, consequently increased the percentage of normal cells. Furthermore PDR significantly inhibited caspase-3 activity in RAECs: this effect is comparable with alpha-tocopherol and more potent than that of L-arginine. In conclusion, PDR is a cell protector. it protects endothelial cell against oxidative injury and apoptosis; its cell protective effect against H(2)O(2) injuries is NOS dependent and is related with NO production; PDR is anti-oxidant, its anti-oxidant effect needs endothelial cell's participation. The findings suggest PDR may play a much better beneficial role than L-arginine in the prevention and treatment for those diseases with endothelial dysfunction. (C) 2008 Elsevier B.V. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/156879 |
| ISSN | 0014-2999 |
| DOI | 10.1016/j.ejphar.2008.09.040 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 药学院 |
