Int J Toxicol 2009,
PMID: 19546257
Peltz, Alon; Sherwani, Shariq I; Kotha, Sainath R; Mazerik, Jessica N; O'Connor Butler, Elizabeth S; Kuppusamy, M Lakshmi; Hagele, Thomas; Magalang, Ulysses J; Kuppusamy, Periannan; Marsh, Clay B; Parinandi, Narasimham L
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.
Diseases/Pathways annotated by Medline MESH: Calcium Signaling
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Text Mining Data
phospholipase D → calmodulin: "
Calcium and
calmodulin regulate mercury induced
phospholipase D activation in vascular endothelial cells
"
PLD → calmodulin: "
Here, we report the novel and significant finding that calcium and calmodulin regulated mercury induced PLD activation in bovine pulmonary artery ECs ( BPAECs )
"
PLD → Calmodulin: "
Calmodulin inhibitors significantly attenuated mercury induced PLD activation in BPAECs
"
Manually curated Databases
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