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Alteration in MARCKS phosphorylation and expression by methylmercury in SH-SY5Y cells and rat brain
Mitsuya Shiraishi1, Makoto Hangai1, Megumi Yamamoto2
1Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
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.
Insights
Methylmercury (MeHg) neurotoxicity involves changes in myristoylated alanine-rich C kinase substrate (MARCKS). MeHg exposure alters MARCKS expression and phosphorylation, impacting neuronal cell death and neurotoxicity.
Area of Science:
- Neuroscience
- Toxicology
- Molecular Biology
Background:
- Methylmercury (MeHg) is a potent neurotoxin, but its precise molecular mechanisms remain unclear.
- Myristoylated alanine-rich C kinase substrate (MARCKS) is crucial for neuronal development and differentiation.
- Understanding MARCKS' role in MeHg neurotoxicity could reveal new therapeutic targets.
Purpose of the Study:
- To investigate the impact of MeHg on MARCKS expression and phosphorylation in neuronal cells and the rat brain.
- To elucidate the role of MARCKS alterations in MeHg-induced neurotoxicity.
Main Methods:
- Utilized neuroblastoma SH-SY5Y cells and rat brain tissue models.
- Assessed cell viability, MARCKS expression, and phosphorylation levels.
- Employed protein kinase C inhibitors, Ca(2+) chelators, and siRNA for MARCKS knockdown.
Main Results:
- MeHg exposure decreased SH-SY5Y cell viability, increased MARCKS phosphorylation, and reduced MARCKS expression.
- Inhibition of protein kinase C or reduction of extracellular Ca(2+) mitigated MeHg-induced MARCKS phosphorylation.
- MARCKS knockdown exacerbated MeHg-induced cell death.
- MARCKS phosphorylation was elevated in the olfactory bulb of MeHg-treated rats.
Conclusions:
- Alterations in MARCKS expression and phosphorylation are implicated in methylmercury neurotoxicity.
- MARCKS plays a protective role against MeHg-induced neuronal damage.
- Targeting MARCKS pathways may offer a strategy to combat MeHg poisoning.
