期刊
INTERNATIONAL JOURNAL OF TOXICOLOGY
卷 28, 期 3, 页码 190-206出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1091581809338077
关键词
calcium; calmodulin; L-type calcium channel blockers; lipid signaling; mercury; phospholipase D; phosphatidic acid; vascular endothelial cells
资金
- Dorothy M. Davis Heart and Lung Research Institute
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine of the Ohio State University College of Medicine
- International Academy of Oral Medicine and Toxicology.
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 mu M; thimerosal, 25 mu M; methylmercury, 10 mu M) 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.
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