Wellthy Choices Network

Posted By Jan Jenson on April 28, 2010

Toxicol Sci. 2010 Apr 26. [Epub ahead of print]

Methylmercury Induces Acute Oxidative Stress, Altering Nrf2 Protein
Level in Primary Microglial Cells.

Ni
M,
Li
X,
Yin
Z,
Jiang
H,
Sidoryk-Wegrzynowi cz
M,
Milatovic
D,
Cai
J,
Aschner
M.

Department of Pharmacology.

Abstract

The neurotoxicity of methylmercury (MeHg) is well documented in both
humans and animals. MeHg causes acute and chronic damage to multiple
organs, most profoundly the central nervous system (CNS). Microglial
cells are derived from macrophage cell linage, making up
approximately 12% of cells in the CNS, yet their role in MeHg-induced
neurotoxicity is not well-defined. The purpose of present study was
to characterize microglial vulnerability to MeHg and their potential
adaptive response to acute MeHg exposure. We examined the effects of
MeHg on microglial viability, reactive oxygen species (ROS)
generation, glutathione (GSH) level, redox homeostasis and Nrf2
protein expression. Our data showed that MeHg (1-5 muM) treatment
caused a rapid (within 1 min) concentration- and time-dependent
increase in ROS generation, accompanied by a statistically
significant decrease in the ratio of GSH and its oxidized form
glutathione disulfide (GSSG) (GSH/GSSG ratio). MeHg increased the
cytosolic Nrf2 protein level within 1 min of exposure, followed by
its nuclear translocation after 10 min of treatment. Consistent with
the nuclear translocation of Nrf2, quantitative real-time PCR
revealed a concentration- dependent increase in the mRNA level of
Ho-1, Nqo1 and xCT 30 min post MeHg exposure, while Nrf2 knockdown
greatly reduced the upregulation of these genes. Furthermore, we
observed increased microglial death upon Nrf2 knockdown by the shRNA
approach. Taken together, our study has demonstrated that microglial
cells are exquisitely sensitive to MeHg and respond rapidly to MeHg
by upregulating the Nrf2-mediated antioxidant response.

PMID: 20421342 [PubMed - as supplied by publisher]

http://www.ncbi. nlm.nih.gov/ pubmed/20421342

Categories: Dental health, Detoxification, Sustainable Living, Vaccinations/vaccines

Tags: acute damage, Acute Oxidative Stress, central nervous system, chronic damage, glutathione (GSH) level, Methylmercury, Microglial cells, neurotoxicity