Alteration in MARCKS phosphorylation and expression by methylmercury in SH-SY5Y cells and rat brain

Mitsuya Shiraishi; Makoto Hangai; Megumi Yamamoto; Masanori Sasaki; Atsuhiro Tanabe; Yasuharu Sasaki; Atsushi Miyamoto

doi:10.1016/j.etap.2014.04.025

Alteration in MARCKS phosphorylation and expression by methylmercury in SH-SY5Y cells and rat brain

Environ Toxicol Pharmacol. 2014 May;37(3):1256-63. doi: 10.1016/j.etap.2014.04.025. Epub 2014 Apr 28.

Authors

Mitsuya Shiraishi¹, Makoto Hangai², Megumi Yamamoto³, Masanori Sasaki³, Atsuhiro Tanabe⁴, Yasuharu Sasaki⁵, Atsushi Miyamoto²

Affiliations

¹ 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.
² Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
³ Department of Basic Medical Sciences, National Institute for Minamata Disease, 4058-18 Hama, Minamata, Kumamoto 867-0008, Japan.
⁴ Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
⁵ Laboratory of Pharmacology, School of Pharmaceutical Science, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.

PMID: 24835554
DOI: 10.1016/j.etap.2014.04.025

Abstract

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.

Keywords: MARCKS; Methylmercury; Neurotoxicity; Phosphorylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / drug effects*
Brain / metabolism
Cell Line, Tumor
Cell Survival / drug effects
Humans
Intracellular Signaling Peptides and Proteins / metabolism*
Male
Membrane Proteins / metabolism*
Methylmercury Compounds / toxicity*
Myristoylated Alanine-Rich C Kinase Substrate
Neurotoxins / toxicity*
Phosphorylation
Rats, Wistar

Substances

Intracellular Signaling Peptides and Proteins
MARCKS protein, human
Marcks protein, rat
Membrane Proteins
Methylmercury Compounds
Neurotoxins
Myristoylated Alanine-Rich C Kinase Substrate