Increased protein SUMOylation following focal cerebral ischemia.
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 6h and 24h in the striatal infarct area and by SUMO-2/3 at 24h 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 6h but there was increased SUMO-1 conjugation in the cortical infarct and non-ischemic hippocampus at 24h 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.
Cimarosti
Helena
H
MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, UK.
Lindberg
Camilla
C
Bomholt
Signe F
SF
Rønn
Lars C B
LC
Henley
Jeremy M
JM
D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology; D003720:Densitometry; D007839:Functional Laterality / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D017072:Neostriatum / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000096:biosynthesis*
D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; D025841:Small Ubiquitin-Related Modifier Proteins; C102718:metabotropic glutamate receptor 3; C113897:metabotropic glutamate receptor 6; C102719:metabotropic glutamate receptor 7; C108823:metabotropic glutamate receptor 4