Folate stimulates ERK1/2 phosphorylation and cell proliferation in fetal neural stem cells.
Cellular events for neural progenitor cells, such as proliferation and differentiation, are regulated by multiple intrinsic and extrinsic cell signals. Folate plays central roles in central nervous system development, so folate, as an extrinsic signal, may affect neural stem cell (NSC) proliferation and differentiation. In this study, we have investigated the effect of folate on extracellular signal-regulated kinase (ERK1/2) phosphorylation, cell proliferation and apoptosis in fetal NSCs. The results showed that treatment of neurospheres with folate increased ERK1/2 phosphorylation and cell proliferation in a concentration-dependent manner. Folate also decreased the percentage of apoptotic cells. All of these effects of folate were prevented by a selective inhibitor (U0126) of mitogen-activated/ERK kinase 1/2. In conclusion, fetal NSCs respond to folate with ERKl/2 phosphorylation, cell proliferation and decreased apoptosis. This mechanism may mediate the regulation by folate of neurogenesis in the central nervous system.
Zhang
Xu-Mei
XM
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China. zhangxumei2008@yahoo.com.cn
Huang
Guo-Wei
GW
Tian
Zhi-Hong
ZH
Ren
Da-Lin
DL
Wilson
John X
JX
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D053686:Fetal Stem Cells / Q000166:cytology / Q000378:metabolism*; D005492:Folic Acid / Q000008:administration & dosage*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D005492:Folic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3