| Title | Calcium and Calmodulin Regulate Mercury-induced Phospholipase D Activation in Vascular Endothelial Cells. | | Author(s) | Peltz A, Sherwani SI, Kotha SR, Mazerik JN, O'Connor Butler ES, Kuppusamy ML, Hagele T, Magalang UJ, Kuppusamy P, Marsh CB, Parinandi NL | | Institution | Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, 473 W. 12 Ave, Columbus, OH 43210; narasimham.parinandi@osumc.edu. | | Source | Int J Toxicol 2009 May-Jun; 28(3):190-206. | | Abstract | Earlier, we reported that mercury, the environmental risk factor for cardiovascular diseases, activates vascular endothelial cell (EC) phospholipase D (PLD). Here, we report the novel and significant finding that calcium and calmodulin regulated mercury-induced PLD activation in bovine pulmonary artery ECs (BPAECs). Mercury (mercury chloride, 25 muM; thimerosal, 25 muM; methylmercury, 10 muM) significantly activated PLD in BPAECs. Calcium chelating agents and calcium depletion of the medium completely attenuated the mercury-induced PLD activation in ECs. Calmodulin inhibitors significantly attenuated mercury-induced PLD activation in BPAECs. Despite the absence of L-type calcium channels in ECs, nifedipine, nimodipine, and diltiazem significantly attenuated mercury-induced PLD activation and cytotoxicity in BPAECs. This study demonstrated the importance of calcium and calmodulin in the regulation of mercury-induced PLD activation and the protective action of L-type calcium channel blockers against mercury cytotoxicity in vascular ECs, suggesting mechanisms of mercury vasculotoxicity and mercury-induced cardiovascular diseases. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19546257 |
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