The influence of methylmercury on the nitric oxide production of alveolar macrophages.
Mercury is a global pollutant considered to be a persistent bioaccumulative and toxic chemical. Humans may be exposed to organic forms of mercury by either inhalation, oral, or dermal routes. Methylmercury is more toxic to living organisms than the inorganic forms. In this study, we attempted to elucidate the altered functions of alveolar macrophage including nitric oxide production after methylmercury exposure. Treatment of 7 muM methylmercury for 24 h inhibited lipopolysaccharide-induced nitric oxide and nitric oxide synthase production of alveolar macrophages. The addition of H-89 (PKA inhibitor) significantly decreased the methylmercury inhibition of lipopolysaccharide-mediated nitric oxide production. We found the cell had a calcium-dependent adenylate cyclase, and MeHg could inhibit the phosphorylation of extracellular-signal regulated kinase (ERK). Because methylmercury could increase the intracellular calcium ion concentration, it might activate the adenylate cyclase by increasing [Ca(2+)](i). Though the interaction of methylmercury with the immune system has been studied by several investigators, the actual mechanisms underlying these interactions are still poorly understood. We discovered that methylmercury could activate protein kinase A, which in turn would inhibit the activation of Raf-1-ERK and so inhibit the release of nitric oxide.
Kuo
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TC
Department of Cosmetic Science, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan. kuotsung@mail.chna.edu.tw
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D007546:Isoquinolines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
D004785:Environmental Pollutants; D007546:Isoquinolines; D008070:Lipopolysaccharides; D008767:Methylmercury Compounds; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D000262:Adenylyl Cyclases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide