Reduced zinc cytotoxicity following differentiation of neural stem/progenitor cells into neurons and glial cells is associated with upregulation of metallothioneins.
We investigated zinc cytotoxicity in mouse neural stem/progenitor cells (NSPCs) and their differentiated progeny (neuronal/glial cells) in correlation with expression of metallothionein (MT) gene. Differentiated cells were less sensitive than NSPCs to ZnCl2 (IC50: 128μM vs. 76μM). Differentiation of immature NSPCs to the differentiated cells led to an increase in expression of MT family genes (Mt1, Mt2, Mt3, and Mt4). Zinc exposure induced a dose-dependent increase in expression level of Mt1 and that of Mt2 in both NSPCs and the differentiated cells. Our results showed that the reduced cytotoxicity of zinc associated with differentiation from NSPCs into their progeny was related to the upregulation of MTs.
Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570, Japan.
Mayu
M
Nishikawa
Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570, Japan.
Hideki
H
Mori
Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570, Japan. Electronic address: hara@b.s.osakafu-u.ac.jp.
Masayuki
M
Hara
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D000090023:Metallothionein 3; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects* / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation; D017967:Zinc Compounds / Q000633:toxicity*
D015415:Biomarkers; D002712:Chlorides; D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D017967:Zinc Compounds; C016837:zinc chloride; D008668:Metallothionein
Astrocyte; Differentiation; Metallothionein; Neural stem cells; Zinc, Cytotoxicity