Calcium and calmodulin regulate mercury-induced phospholipase D activation in vascular endothelial cells.

Author: Peltz A, Sherwani SI, Kotha SR, Mazerik JN, O'Connor Butler ES, Kuppusamy ML, Hagele T, Magalang UJ, Kuppusamy P, Marsh CB, Parinandi NL.

Source: Int J Toxicol.

Year: 2009

Comment:

Abstract / Excerpt:

“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.”

Citation:

Peltz A, Sherwani SI, Kotha SR, Mazerik JN, O'Connor Butler ES, Kuppusamy ML, Hagele T, Magalang UJ, Kuppusamy P, Marsh CB, Parinandi NL. Calcium and calmodulin regulate mercury-induced phospholipase D activation in vascular endothelial cells. Int J Toxicol. 2009; 28(3):190-206.