title: MARCKS is involved in methylmercury-induced decrease in cell viability and nitric oxide production in EA.hy926 cells.
abstract: Methylmercury (MeHg) is a persistent environmental contaminant that has been reported worldwide. MeHg exposure has been reported to lead to increased risk of cardiovascular diseases; however, the mechanisms underlying the toxic effects of MeHg on the cardiovascular system have not been well elucidated. We have previously reported that mice exposed to MeHg had increased blood pressure along with impaired endothelium-dependent vasodilation. In this study, we investigated the toxic effects of MeHg on a human endothelial cell line, EA.hy926. In addition, we have tried to elucidate the role of myristoylated alanine-rich C kinase substrate (MARCKS) in the MeHg toxicity mechanism in EA.hy926 cells. Cells exposed to MeHg (0.1-10 µM) for 24 hr showed decreased cell viability in a dose-dependent manner. Treatment with submaximal concentrations of MeHg decreased cell migration in the wound healing assay, tube formation on Matrigel and spontaneous nitric oxide (NO) production of EA.hy926 cells. MeHg exposure also elicited a decrease in MARCKS expression and an increase in MARCKS phosphorylation. MARCKS knockdown or MARCKS overexpression in EA.hy926 cells altered not only cell functions, such as migration, tube formation and NO production, but also MeHg-induced decrease in cell viability and NO production. These results suggest the broad role played by MARCKS in endothelial cell functions and the involvement of MARCKS in MeHg-induced toxicity.
authors.affiliation: Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Cuong
authors.initials: C
authors.lastname: VAN Dao
authors.forename: Md Zahorul
authors.initials: MZ
authors.lastname: Islam
authors.forename: Kasumi
authors.initials: K
authors.lastname: Sudo
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Shiraishi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000633:toxicity*; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009569:Nitric Oxide / Q000096:biosynthesis*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; C000619711:Marcks protein, mouse; D008565:Membrane Proteins; D008767:Methylmercury Compounds; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009569:Nitric Oxide