Transient global cerebral ischemia induces a massive increase in protein sumoylation

W Yang, H Sheng, DS Warner… - Journal of Cerebral …, 2008 - journals.sagepub.com
W Yang, H Sheng, DS Warner, W Paschen
Journal of Cerebral Blood Flow & Metabolism, 2008journals.sagepub.com
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 …
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-κB (NF-κB) essential modulator where sumoylation leads to an activation of NF-κB. 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.
Sage Journals