Transient global cerebral ischemia induces a massive increase in protein sumoylation

J Cereb Blood Flow Metab. 2008 Feb;28(2):269-79. doi: 10.1038/sj.jcbfm.9600523. Epub 2007 Jun 13.

Abstract

A new group of proteins, small ubiquitin-like modifier (SUMO) proteins, has recently been identified and protein sumoylation has been shown to play a major role in various signal transduction pathways. Here, we report that transient global cerebral ischemia induces a marked increase in protein sumoylation. Mice were subjected to 10 mins severe forebrain ischemia followed by 3 or 6 h of reperfusion. Transient cerebral ischemia induced a massive increase in protein sumoylation by SUMO2/3 both in the hippocampus and cerebral cortex. SUMO2/3 conjugation was associated with a decrease in levels of free SUMO2/3. After ischemia, protein levels of the SUMO-conjugating enzyme Ubc9 were transiently decreased in the cortex but not in the hippocampus. We also exposed HT22 cells to arsenite, a respiratory poison that impairs cytoplasmic function and induces oxidative stress. Arsenite exposure induced a marked rise in protein sumoylation, implying that impairment of cytoplasmic function and oxidative stress may be involved in the massive post-ischemic activation of SUMO conjugation described here. Sumoylation of transcription factors has been shown to block their activation, with some exceptions such as the heat-shock factor and the hypoxia-responsive factor, where sumoylation blocks their degradation, and the nuclear factor-kappaB (NF-kappaB) essential modulator where sumoylation leads to an activation of NF-kappaB. Because protein sumoylation is known to be involved in the regulation of various biologic processes, the massive post-ischemic increase in protein sumoylation may play a critical role in defining the final outcome of neurons exposed to transient ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cells, Cultured
  • Endopeptidases / metabolism
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Ischemic Attack, Transient / metabolism*
  • Male
  • Mice
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Small Ubiquitin-Related Modifier Proteins / biosynthesis*
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Ubiquitin-Conjugating Enzymes / biosynthesis
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitins / metabolism

Substances

  • RNA, Messenger
  • SUMO2 protein, mouse
  • Small Ubiquitin-Related Modifier Proteins
  • Sumo3 protein, mouse
  • Ubiquitins
  • Ubiquitin-Conjugating Enzymes
  • Endopeptidases
  • Senp1 protein, mouse
  • ubiquitin-conjugating enzyme UBC9