Transient global cerebral ischemia induces a massive increase in protein sumoylation.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Yang, W; Sheng, H; Warner, DS; Paschen, W

Published Date

  • February 2008

Published In

Volume / Issue

  • 28 / 2

Start / End Page

  • 269 - 279

PubMed ID

  • 17565359

International Standard Serial Number (ISSN)

  • 0271-678X

Digital Object Identifier (DOI)

  • 10.1038/sj.jcbfm.9600523


  • eng

Conference Location

  • United States