Polyaspartoyl l-arginine protects endothelial cells against injury.
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 microg/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 microg/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 microg/ml) raised nitrite level in RAEC medium, which is the major end-product of NO, but l-arginine (170 microg/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 microg/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.
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Yang
Y
Jian
Zhiyu
Z
Tang
Yinye
Y
Wang
Shiqi
S
Peng
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000166:cytology / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006861:Hydrogen Peroxide; D008077:Lipoproteins, LDL; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D024502:alpha-Tocopherol / Q000494:pharmacology
D000975:Antioxidants; D005343:Fibrinolytic Agents; D008077:Lipoproteins, LDL; D010455:Peptides; C099252:oxidized low density lipoprotein; C483710:polyaspartoyl-L-arginine; D009569:Nitric Oxide; D001120:Arginine; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D024502:alpha-Tocopherol