Effects of low level of methylmercury on proliferation of cortical progenitor cells.
Methylmercury (MeHg) is a potent environmental neurotoxin that shows toxicity to developing central nervous system (CNS), causing brain damage in children even at low exposure levels. However, the mechanisms for its effect on CNS are not well understood. In current study, primary cultures of progenitor cells from embryonic cerebral cortex were used as a model system to study the potential effect and the underlying mechanism of MeHg on neural progenitor cells. Results showed that, in cultured cortical progenitor cells, 48-h exposure to low-level of MeHg (at 2.5 nM, 5 nM and 50 nM, respectively) caused G1/S cell cycle arrest in a dose-dependent manner without inducing cell death. Interestingly, the expression of cyclin E, which promotes G1/S transition, but not cyclin D1 and CDK2, was selectively downregulated by exposure of MeHg. In addition, low-level of MeHg inhibited the maintenance of ERK1/2 phosphorylation, possibly by abolishing the late phase ERK1/2 activation induced by bFGF. Thus, MeHg may induce proliferation inhibition and cell cycle arrest of neural progenitor cells via regulating cyclin E expression and perturbing a pathway that involves ERK1/2.
Xu
Mingyu
M
XinHua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai Key Laboratory of Children's Environmental Health, Shanghai 200092, China.
Yan
Chonghuai
C
Tian
Ying
Y
Yuan
Xiaobing
X
Shen
Xiaoming
X
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D019927:Cyclin E / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D008767:Methylmercury Compounds / Q000633:toxicity*; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D019927:Cyclin E; D008767:Methylmercury Compounds; D048049:Extracellular Signal-Regulated MAP Kinases; C004925:methylmercuric chloride