Effect of methylmercury (CH3HgCl) injury on nitric oxide synthase (NOS) activity in cultured human umbilical vascular endothelial cells.
The effects of methylmercury (CH3HgCl; MeHg) on the production of nitric oxide (NO) and the activity of the enzyme, nitric oxide synthase (NOS), in cultured human umbilical vascular endothelial cells (HUVEC) were examined. To assess the production of NO by HUVEC, platelet aggregation experiments were performed using cuvettes lined with HUVEC. Thrombin (0.05 U/ml)-induced platelet aggregation was inhibited in HUVEC pretreated with indomethacin (1 microM), an inhibitor of the cyclo-oxygenase pathway. The anti-platelet aggregatory effect of HUVEC treated with indomethacin was decreased dose-dependently by 48-h pretreatment with MeHg (0.5-2 microM). The effect of MeHg on the NADPH diaphorase staining of NOS in HUVEC showed dose-dependent cytotoxicity in regard to NOS activity. These findings suggest that MeHg inhibits the production of NO by HUVEC, an action which may be dependent on the cytotoxic effect exerted by MeHg on NOS activity.
Department of Environmental Medicine, Shimane Medical University, Izumo, Japan.
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Kishimoto
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Oguri
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Tada
D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008767:Methylmercury Compounds / Q000633:toxicity*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D013194:Staining and Labeling; D013917:Thrombin / Q000633:toxicity; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D016861:Cyclooxygenase Inhibitors; D008767:Methylmercury Compounds; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013917:Thrombin; D007213:Indomethacin