Methylmercury Inhibits Nitric Oxide Production Mediated by Ca super(2+) Overload and Protein Kinase A Activation
Neutrophils from male ICR mice were incubated with methylmercury (MeHg), and effects on nitric oxide production mediated by intracellular calcium (Cai) overload and protein kinase A activation were determined. The data showed that the presence of MeHg increased Cai markedly, reaching steady state af...
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Published in | Toxicology (Amsterdam) Vol. 176; no. 1; p. 113 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
01.07.2002
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Online Access | Get full text |
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Summary: | Neutrophils from male ICR mice were incubated with methylmercury (MeHg), and effects on nitric oxide production mediated by intracellular calcium (Cai) overload and protein kinase A activation were determined. The data showed that the presence of MeHg increased Cai markedly, reaching steady state after 300 s in a MeHg concentration-dependent manner. A MeHg concentration of 5 mu M inhibited lipopolysaccharide-induced NO generation. The Ca channel blocker, verapamil, antagonized the increase in Cai produced by MeHg in the presence of Ca, while an inhibitor of protein kinase A had an opposite effect on MeHg-inhibited NO production. The data suggested that MeHg activated protein kinase A through the Ca-activated adenylate cyclase cyclic AMP pathway, which inhibits NO synthase gene expression via raf protein-phosphorylation. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0300-483X |