Selenoprotein H is a redox-sensing high mobility group family DNA-binding protein that up-regulates genes involved in glutathione synthesis and phase II detoxification

J Biol Chem. 2007 Aug 17;282(33):23759-65. doi: 10.1074/jbc.M702267200. Epub 2007 May 25.

Abstract

Selenoprotein H is a recently identified member of the selenoprotein family whose function is not fully known. Previous studies from our laboratory and others showed that Drosophila melanogaster selenoprotein H is essential for viability and antioxidant defense. In this study we investigated the function of human selenoprotein H in murine hippocampal HT22 cells engineered to stably overexpress the protein. After treatment of cells with L-buthionine-(S,R)-sulfoximine to deplete glutathione, selenoprotein H-overexpressing cells exhibited higher levels of total glutathione, total antioxidant capacities, and glutathione peroxidase enzymatic activity than did vector control cells. Overexpression of selenoprotein H also up-regulated the mRNA levels of endogenous selenoprotein H, glutamylcysteine synthetase heavy and light chains, and glutathione S-transferases Alpha 2, Alpha 4, and Omega 1. The amino acid sequence of selenoprotein H contains four putative nuclear localization sequences and an AT-hook motif, a small DNA-binding domain first identified in high mobility group proteins. Chromatin immunoprecipitation using a green fluorescent protein-selenoprotein H fusion revealed binding to sequences containing heat shock and/or stress response elements. Thus, selenoprotein H is a redox-responsive DNA-binding protein of the AT-hook family and functions in regulating expression levels of genes involved in de novo glutathione synthesis and phase II detoxification in response to redox status.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation, Enzymologic*
  • Glutathione / biosynthesis*
  • High Mobility Group Proteins
  • Hippocampus / cytology
  • Humans
  • Metabolic Detoxication, Phase II / genetics*
  • Mice
  • Oxidation-Reduction
  • Selenoproteins / physiology*
  • Up-Regulation / genetics

Substances

  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Selenoproteins
  • selenoprotein H, human
  • Glutathione