Calcium and calmodulin regulate mercury-induced phospholipase D activation in vascular endothelial cells.
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.
Peltz
Alon
A
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.
Sherwani
Shariq I
SI
Kotha
Sainath R
SR
Mazerik
Jessica N
JN
O'Connor Butler
Elizabeth S
ES
Kuppusamy
M Lakshmi
ML
Hagele
Thomas
T
Magalang
Ulysses J
UJ
Kuppusamy
Periannan
P
Marsh
Clay B
CB
Parinandi
Narasimham L
NL
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*
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