Extremely low-frequency electromagnetic field promotes astrocytic differentiation of human bone marrow mesenchymal stem cells by modulating SIRT1 expression

Biosci Biotechnol Biochem. 2017 Jul;81(7):1356-1362. doi: 10.1080/09168451.2017.1308243. Epub 2017 Mar 29.

Abstract

It has been shown that extremely low-frequency electromagnetic fields (ELFMF) affect regulation of cell fate and differentiation. Thus, the aim of this study was to investigate the role of ELFMFs in the enhancement of astrocytic differentiation. ELFMF exposure reduced the rate of proliferation and enhanced astrocytic differentiation. The ELFMF-treated cells showed increased levels of the astrocyte marker (GFAP), while those of the early neuronal marker (Nestin) and stemness marker (OCT3/4) were downregulated. The reactive oxygen species (ROS) level was observed to be significantly elevated after ELFMF exposure, which strengthens the modulatory role of SIRT1 and SIRT1 downstream molecules (TLE1, HES1, and MASH1) during astrocytic differentiation. After nicotinamide (5 mM) mediated inhibition of SIRT1, levels of TLE1, HES1, and MASH1 were examined; TLE1 was significantly upregulated and MASH1 was downregulated. These results suggest that ELFMFs induce astrocytic differentiation through activation of SIRT1 and SIRT1 downstream molecules.

Keywords: SIRT1; TLE1; astrocytic differentiation; extremely low-frequency electromagnetic fields; hBM-MSCs.

MeSH terms

  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism*
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Co-Repressor Proteins
  • Electromagnetic Fields*
  • Gene Expression Regulation
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Nestin / genetics
  • Nestin / metabolism
  • Neurogenesis / genetics
  • Niacinamide / pharmacology
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Reactive Oxygen Species / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Sirtuin 1 / antagonists & inhibitors
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Transcription Factor HES-1 / genetics
  • Transcription Factor HES-1 / metabolism

Substances

  • ASCL1 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Co-Repressor Proteins
  • Glial Fibrillary Acidic Protein
  • NES protein, human
  • Nestin
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Reactive Oxygen Species
  • Repressor Proteins
  • TLE1 protein, human
  • Transcription Factor HES-1
  • HES1 protein, human
  • Niacinamide
  • SIRT1 protein, human
  • Sirtuin 1