Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyaspartoyl.l-arginine (PDR) is an inhibitor of platelet aggregation ex vivo but in vitro. This study attempts to elucidate the target cell of PDR action and its action mechanism. PDR (1.7-170 microg/ml) significantly inhibited platelet aggregation in vitro in the presence of rat aortic endothelial cells (RAEC), NO synthase inhibitor N-nitro-l-arginine methyl ester (l-NAME) inhibited this effect, but it was ineffective in the RAEC absence. Correspondingly, PDR increased NO level in the supernatants of the platelet reactants in RAEC presence, but failed to influence NO level in RAEC absence, and these effects of PDR were more potent than those of l-arginine. Furthermore, PDR markedly elevated the intracellular level of l-arginine, and it (17-170 microg/ml) also augmented l-citrulline level in RAEC, argininosuccinate lyase (ASL) inhibitor succinate enhanced its effect on l-citrulline but l-NAME weakened it. 170 microg/ml of PDR slightly increased the l-aspartate level in RAEC, and succinate enhanced this effect. However l-arginine, l-aspartate or the combination of l-arginine and l-aspartate failed to change levels of these amino acids. In addition, PDR (170 microg/ml) stimulated the expression of argininosuccinate synthetase (ASS) protein. In conclusion, the endothelial cell is direct target cell of PDR's action; PDR facilitates the entry of l-arginine by serving as a carrier of l-arginine into RAEC; it also supplies aspartic acid and stimulates ASS expression, and then enhances the intracellular citrulline-NO cycle, thus increases the availability of l-arginine and NO synthesis. Therefore the effect of PDR on platelet aggregation is primarily attributed to its stimulation of NO synthesis in endothelial cells; PDR may be a better cardiovascular protective agent than l-arginine.
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PMID:Polyaspartoyl.l-arginine inhibits platelet aggregation through stimulation of NO release from endothelial cells. 1845 31

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.
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PMID:Polyaspartoyl l-arginine protects endothelial cells against injury. 1885 83

Nitric oxide (NO) and prostacyclin (PGI(2)) are two of the most important vasodilators produced by endothelial cells, the regulation of NO on PGI(2) production has not been fully clear yet. Polyaspartoyl.L-arginine (PDR) is an L-arginine residue-rich compound with inhibitory effects of platelet aggregation and thrombosis. This study investigated its effects on NO production in rat aortic endothelial cells (RAECs) and observed the influence of NO on PGI(2) level in RAECs. NO concentration in the medium of RAECs was assessed with fluorometric method; 6-keto-PGF(1 alpha), the stable metabolite of PGI(2), in the medium of RAECs was measured with radioimmunoassay kits; Protein level of PGI(2) synthase in RAECs was determined by Western blot analysis. PDR (17.0 approximately 170 microg/ml, equal to 0.5 microM-5 microM) enhanced NO level in culture medium of RAEC with concentration-dependent manner (P<0.01); L-arginine (170 microg/ml, equal to 1000 microM) and 1.70 microg/ml (0.05 microM) of PDR slightly increased NO level (P>0.05). Interestingly PDR (1.70-500 microg/ml), L-arginine (17.0-170 microg/ml) significantly elevated PGI(2) levels in medium of RAECs (P<0.01), NO synthase inhibitor, N(G)-nitro L-arginine methyl ester (L-NAME), markedly inhibited the elevated PGI(2) levels by PDR and L-arginine. NO donor, sodium nitroprusside(SNP)(1-500 microM), showed the most powerful effects of increasing PGI(2) level in RAECs, which was not influenced by L-NAME. Cyclooxigenase(COX) inhibitor, indomethacin, significantly reduced elevated PGI(2) level by both PDR and SNP in RAEC medium. PDR (170 microg/ml) increased the expression of PGI(2) synthase, L-NAME partly inhibited this effect. In conclusion, PDR enhances PGI(2) synthesis in RAEC, which is attributed to its effect of NO production; the stimulating effect of PDR on PGI(2) synthesis may be mediated via COX and PGI(2) synthase.
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PMID:Polyaspartoyl.L-arginine enhances prostacyclin synthesis in rat aortic endothelial cells. 1902 30