title: Extremely low-frequency electromagnetic field induces neural differentiation of hBM-MSCs through regulation of (Zn)-metallothionein-3.
abstract: Extremely low-frequency electromagnetic field (ELFEMF) can stimulate neural differentiation in human bone marrow-derived mesenchymal cells (hBM-MSCs), and this provides an opportunity for research on neurodegenerative diseases such as Alzheimer's disease (AD). Metallothionein-3 (MT3), an isoform of the metal-binding proteins, metallothioneins, involved in maintaining intracellular zinc (Zn) homeostasis and the deregulation of zinc homeostasis, has separately been implicated in AD. Here, we investigated the effect of ELFEMF-induced neural differentiation of hBM-MSCs on Zn-MT3 homeostatic interaction. Exposure to ELFEMF induced neural differentiation of hBM-MSCs, which was characterized by decreased proliferation and enhanced neural-like morphology. We observed expression of neuronal markers such as β-tubulin3, pleiotrophin, and neurofilament-M at the mRNA level and MAP2 at the protein level. ELFEMF-induced neural differentiation correlated with decreased expression of metal-response element-transcription factor 1 and MT3, as well as decreased intracellular Zn concentration. In addition, upregulation of dihydropyrimidinase-related protein 2 was observed, but there was no change in γ-enolase expression. These data indicate a possible regulatory mechanism for MT3 during neural differentiation. Our findings provide considerable insight into molecular mechanisms involved in neural differentiation, which is useful for developing new treatments for neurodegenerative diseases. Bioelectromagnetics. 38:364-373, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.|Department of Biochemistry, Cell and Molecular Biology, School of Biological Sciences, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana.
authors.forename: Anastasia Rosebud
authors.initials: AR
authors.lastname: Aikins
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Hong
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Seoul Center, Korea Basic Science Institute, Seoul, Korea.
authors.forename: Cheol-Ho
authors.initials: CH
authors.lastname: Yoon
authors.affiliation: Seoul Center, Korea Basic Science Institute, Seoul, Korea.
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: Chung
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: MiJung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Chan-Wha
authors.initials: CW
authors.lastname: Kim
mesh_terms: D002454:Cell Differentiation / Q000528:radiation effects*; D015536:Down-Regulation / Q000528:radiation effects; D004574:Electromagnetic Fields; D006706:Homeostasis / Q000528:radiation effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000528:radiation effects*
chemical_list: D008668:Metallothionein
keywords: Alzheimer's disease; HPLC-ICP-MS; intracellular zinc homeostasis; metal-binding proteins; neural markers