title: Calcium and calmodulin regulate mercury-induced phospholipase D activation in vascular endothelial cells.
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 microM; thimerosal, 25 microM; methylmercury, 10 microM) 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.
authors: 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, USA.
authors: Alon
authors: A
authors: Peltz
authors: Shariq I
authors: SI
authors: Sherwani
authors: Sainath R
authors: SR
authors: Kotha
authors: Jessica N
authors: JN
authors: Mazerik
authors: Elizabeth S
authors: ES
authors: O'Connor Butler
authors: M Lakshmi
authors: ML
authors: Kuppusamy
authors: Thomas
authors: T
authors: Hagele
authors: Ulysses J
authors: UJ
authors: Magalang
authors: Periannan
authors: P
authors: Kuppusamy
authors: Clay B
authors: CB
authors: Marsh
authors: Narasimham L
authors: NL
authors: Parinandi
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002417:Cattle; D016923:Cell Death; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation; D008627:Mercuric Chloride / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D010739:Phospholipase D / Q000378:metabolism*; D013849:Thimerosal / Q000633:toxicity*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002147:Calmodulin; D002614:Chelating Agents; D008767:Methylmercury Compounds; D013849:Thimerosal; D008627:Mercuric Chloride; D010739:Phospholipase D; C004925:methylmercuric chloride; D002118:Calcium