Glutathione peroxidase-1 is required for self-renewal of murine embryonic stem cells

Biochem Biophys Res Commun. 2014 Jun 13;448(4):454-60. doi: 10.1016/j.bbrc.2014.04.139. Epub 2014 May 4.

Abstract

Embryonic stem (ES) cells are pluripotent cells that are capable of giving rise to any type of cells in the body and possess unlimited self-renewal potential. However, the exact regulatory mechanisms that govern the self-renewal ability of ES cells remain elusive. To understand the immediate early events during ES cell differentiation, we performed a proteomics study and analyzed the proteomic difference in murine ES cells before and after a 6-h spontaneous differentiation. We found that the expression level of glutathione peroxidase-1 (GPx-1), an antioxidant enzyme, is dramatically decreased upon the differentiation. Both knockdown of GPx-1 expression with shRNA and inhibiting GPx-1 activity by inhibitor led to the differentiation of ES cells. Furthermore, we showed that during early differentiation, the quick degradation of GPx-1 was mediated by proteasome. Thus, our data indicated that GPx-1 is a key regulator of self-renewal of murine embryonic stem cells.

Keywords: Differentiation; Embryonic stem cells; Glutathione peroxidase-1; Self-renewal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Line
  • Cell Proliferation / drug effects
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / enzymology*
  • Enzyme Inhibitors / pharmacology
  • Gene Knockdown Techniques
  • Glutathione Peroxidase / antagonists & inhibitors
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism*
  • Glutathione Peroxidase GPX1
  • Leupeptins / pharmacology
  • Mice
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / drug effects
  • Pluripotent Stem Cells / enzymology
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors / pharmacology
  • RNA, Small Interfering / genetics
  • Thiomalates / pharmacology

Substances

  • Enzyme Inhibitors
  • Leupeptins
  • Proteasome Inhibitors
  • RNA, Small Interfering
  • Thiomalates
  • 2-thiomalic acid
  • Glutathione Peroxidase
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde
  • Glutathione Peroxidase GPX1
  • Gpx1 protein, mouse