Regulation of NO from endothelial cells by the decrease of cellular cAMP under arsenite exposure.
In an attempt to delineate the direct effect of arsenite-induced endothelial dysfunction on nitric oxide (NO) production, confluent bovine aortic endothelial cells (BAEC) were incubated with arsenite, and endothelial NO synthase expression and NO production were measured. Exposure of arsenite decreased NO production for up to 24 h. This decrease was accompanied by decreases in cAMP, protein kinase A (PKA) activity, and furthermore, significant reduction of pCREB. In conclusion, this study is the first to demonstrate that exposure of arsenite decreases NO production by a reduction of pCREB and PKA activity that may be mediated by cAMP, leading to endothelial dysfunction.
Lee
Soo Youn
SY
Division of Environmental and Chemical Engineering, Chonbuk National University, Jeonju 561-756, Korea.
Min
Jiho
J
D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism
D018053:Arsenites; D017362:Cyclic AMP Response Element-Binding Protein; D009569:Nitric Oxide; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D017868:Cyclic AMP-Dependent Protein Kinases; C015001:arsenite