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

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.

• Authors: Wei Yang, Huaxin Sheng, David S Warner, Wulf Paschen
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 28 Issue 2 Pg. 269-79 (Feb 2008) ISSN: 0271-678X [Print] United States
• PMID: 17565359 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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