Cerebral ischemia immediately increases serine phosphorylation of the synaptic RAS-GTPase activating protein SynGAP by calcium/calmodulin-dependent protein kinase II alpha in hippocampus of rats.
The interaction between translocated calcium/calmdulin-dependent protein kinase IIalpha (CaMK IIalpha) and SynGAP during brain ischemia was investigated by Western blotting and immunoprecipitation. Brain ischemia was induced by the four-vessel occlusion method on Sprague-Dawley rats. After 3 min global ischemia, both the binding of CaMK IIalpha to SynGAP and the serine phosphorylation of SynGAP all dramatically increased. Administrating KN-62 through cerebral ventricle (20 min before ischemia) not only remarkably decreased the binding of CaMK IIalpha to SynGAP but also attenuate the elevated serine phosphorylation of SynGAP following 20 min ischemia in hippocampus. These results suggest that CaMK IIalpha is responsible for the serine phosphorylation of SynGAP and a consequent phosphorylation and inhibition of SynGAP may result in activation of mitogen-activated protein kinase pathway which could serve a protective function in brain ischemia.
Song
Bo
B
Research Center of Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou 221002, Jiangsu, PR China.
Meng
Fanjie
F
Yan
Xuebo
X
Guo
Jun
J
Zhang
Guangyi
G
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology* / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D012694:Serine / Q000378:metabolism; D013569:Synapses / Q000201:enzymology*; D015854:Up-Regulation / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D020690:GTPase-Activating Proteins; C112202:Syngap1 protein, rat; D012694:Serine; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517675:Camk2a protein, rat; D018631:ras Proteins