Alteration in MARCKS phosphorylation and expression by methylmercury in SH-SY5Y cells and rat brain.
The molecular mechanisms mediating methylmercury (MeHg)-induced neurotoxicity are not completely understood. Because myristoylated alanine-rich C kinase substrate (MARCKS) plays an essential role in the differentiation and development of neuronal cells, we studied the alteration of MARCKS expression and phosphorylation in MeHg-induced neurotoxicity of neuroblastoma SH-SY5Y cells and in the rat brain. Exposure to MeHg induced a decrease in cell viability of SH-SY5Y cells, which was accompanied by a significant increase in phosphorylation and a reduction in MARCKS expression. Pretreatment of cells with a protein kinase C inhibitor or an extracellular Ca(2+) chelator suppressed MeHg-induced MARCKS phosphorylation. In MARCKS knock-down cells, MeHg-induced cell death was significantly augmented in comparison to control siRNA. In brain tissue from MeHg-treated rats, MARCKS phosphorylation was enhanced in the olfactory bulb in comparison to control rats. The present study may indicate that alteration in MARCKS expression or phosphorylation has consequences for MeHg-induced neurotoxicity.
Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan. Electronic address: shira-m@vet.kagoshima-u.ac.jp.
Mitsuya
M
Shiraishi
Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
Makoto
M
Hangai
Department of Basic Medical Sciences, National Institute for Minamata Disease, 4058-18 Hama, Minamata, Kumamoto 867-0008, Japan.
Megumi
M
Yamamoto
Department of Basic Medical Sciences, National Institute for Minamata Disease, 4058-18 Hama, Minamata, Kumamoto 867-0008, Japan.
Masanori
M
Sasaki
Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
Atsuhiro
A
Tanabe
Laboratory of Pharmacology, School of Pharmaceutical Science, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Yasuharu
Y
Sasaki
Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
Atsushi
A
Miyamoto
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000633:toxicity*; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009498:Neurotoxins / Q000633:toxicity*; D010766:Phosphorylation; D017208:Rats, Wistar
D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; C000619712:Marcks protein, rat; D008565:Membrane Proteins; D008767:Methylmercury Compounds; D009498:Neurotoxins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate
MARCKS; Methylmercury; Neurotoxicity; Phosphorylation