alpha CaMKII is differentially regulated in brain regions that exhibit differing sensitivities to ischemia and excitotoxicity

作者：Skelding Kathryn A; Spratt Neil J; Fluechter Lisa; Dickson Phillip W; Rostas John A P^*

来源：Journal of Cerebral Blood Flow and Metabolism, 2012, 32(12): 2181-2192.

DOI：10.1038/jcbfm.2012.124

• CaMKII
• excitotoxicity
• focal ischemia
• protein phosphorylation

Different brain regions exhibit differing sensitivities to ischemia/excitotoxicity. Whether these differences are due to perfusion or intrinsic factors has not been established. Herein, we found no apparent association between sensitivity to ischemia/excitotoxicity and the level of expression or basal phosphorylation of calcium/calmodulin-stimulated protein kinase II (alpha CaMKII) or glutamate receptors. However, we demonstrated significant differences in CaMKII-mediated responses after ischemia/excitotoxic stimulation in striatum and cortex. In vivo ischemia and in vitro excitotoxic stimulation produced more rapid phosphorylation of Thr253-alpha CaMKII in striatum compared with cortex, but equal rates of Thr286-alpha CaMKII phosphorylation. Phosphorylation by CaMKII of Ser831-GluA1 and Ser1303-GluN2B occurred more rapidly in striatum than in cortex after either stimulus. The differences between brain regions in CaMKII activation and its effects were not accounted for by differences in the expression of alpha CaMKII, glutamate receptors, or density of synapses. These results implicate intrinsic tissue differences in Thr253-alpha CaMKII phosphorylation in the differential sensitivities of brain regions to ischemia/excitotoxicity. Journal of Cerebral Blood Flow and Metabolism (2012) 32, 2181-2192; doi:10.1038/jcbfm.2012.124; published online 29 August 2012

• 出版日期2012-12