O-linked β-N-acetylglucosamine modification of proteins is activated in post-ischemic brains of young but not aged mice: Implications for impaired functional recovery from ischemic stress

J Cereb Blood Flow Metab. 2016 Feb;36(2):393-8. doi: 10.1177/0271678X15608393. Epub 2015 Sep 30.

Abstract

To evaluate the effect of age on the response of brains to an ischemic challenge, we subjected young and aged mice to transient forebrain ischemia, and analyzed the heat shock response and unfolded protein response, ubiquitin conjugation and SUMO conjugation, and O-linked β-N-acetylglucosamine modification of proteins (O-GlcNAcylation). The most prominent age-related difference was an inability of aged mice to activate O-GlcNAcylation. Considering many reports on the protective role of O-GlcNAcylation in various stress conditions including myocardial ischemia, this pathway could be a promising target for therapeutic intervention to improve functional recovery of aged patients following brain ischemia.

Keywords: Aging; O-GlcNAc modification; SUMO conjugation; brain ischemia; ubiquitin conjugation; unfolded protein response.

Publication types

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

MeSH terms

  • Acetylglucosamine / metabolism*
  • Aging / pathology*
  • Animals
  • Brain / pathology*
  • Brain Ischemia / genetics*
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Brain Ischemia / psychology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Ischemia / genetics
  • Myocardial Ischemia / physiopathology
  • Protein Processing, Post-Translational / genetics*
  • Psychomotor Performance
  • Recovery of Function
  • SUMO-1 Protein / metabolism
  • Stress, Physiological / genetics
  • Stroke / pathology*
  • Stroke / psychology*
  • Ubiquitination
  • Unfolded Protein Response / genetics

Substances

  • SUMO-1 Protein
  • Acetylglucosamine