Journal
NEUROPHARMACOLOGY
Volume 54, Issue 2, Pages 280-289Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2007.09.010
Keywords
SUMO; ischemia; stroke; kainate receptor; AMPA receptor; posttranslational modification
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Funding
- MRC [G0601810] Funding Source: UKRI
- Medical Research Council [G0601810] Funding Source: researchfish
- Medical Research Council [G0601810] Funding Source: Medline
- Wellcome Trust [019063] Funding Source: Medline
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Stroke is a major cause of death and disability, which involves excessive glutamate receptor activation leading to excitotoxic cell death. We recently reported that SUMOylation can regulate kainate receptor (KAR) function. Here we investigated changes in protein SUMOylation and levels of KAR and AMPA receptor subunits in two different animal stroke models: a rat model of focal ischemia with reperfusion and a mouse model without reperfusion. In rats, transient middle cerebral artery occlusion (MCAO) resulted in a striatal and cortical infarct. A dramatic increase in SUMOylation by both SUMO-1 and SUMO-2/3 was observed at 6 h and 24 h in the striatal infarct area and by SUMO-2/3 at 24 h in the hippocampus, which was not directly subjected to ischemia. In mice, permanent MCAO resulted in a selective cortical infarct. No changes in SUMOylation occurred at 6 h but there was increased SUMO-1 conjugation in the cortical infarct and non-ischemic hippocampus at 24 h after MCAO. Interestingly, SUMOylation by SUMO-2/3 occurred only outside the infarct area. In both rat and mouse levels of KARs were only decreased in the infarct regions whereas AMPARs were decreased in the infarct and in other brain areas. These results suggest that posttranslational modification by SUMO and down-regulation of AMPARs and KARs may play important roles in the pathophysiological response to ischemia. (C) 2007 Elsevier Ltd. All rights reserved.
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