Hyperglycemia increased brain ischemia injury through extracellular signal-regulated protein Kinase.
This study was to examine the alterations in the phosphorylation of mitogen-activated protein kinase (MAPK) family in transient brain ischemia under a hyperglycemia and to highlight the molecular mechanisms by which hyperglycemia exacerbates brain damage resulting from stroke. Extracellular signal-regulated protein kinase (ERK) expression was studied in rats subjected to global brain ischemia with pre-ischemic normoglycemic (CIN) and hyperglycemic (CIH) conditions. In another group, the hyperglycemic ischemic rats were pretreated with ERK inhibitor U0126 (U0126). Increased phospho-ERK1/2 immunoreactive neurons in the cingulate cortex and hippocampal CA3 were detected in CIN after ischemia and reperfusion. The numbers of phospho-ERK1/2-positive neurons were further increased significantly in CIH compared to the CIN. Pretreatment with U0126 in CIH rats significantly decreased ERK1/2 immunoreactive cells. Western blot analyses confirmed that phospho-ERK1/2 increased significantly after 30 min ischemia and reperfusion compared to non-ischemic controls in both the CIN and CIH groups. The increase of phospho-ERK1/2 was more prominent in the CIH than in the CIN group after 3 and 6h of reperfusion. Treatment with U0126 significantly reduced phospho-ERK1/2 in the CIH group. The findings presented here suggest that ERK1/2 may play a role in mediating neuronal cells death under hyperglycemic condition.
Zhang
Jian-Zhong
JZ
Institute of Immunopathology, School of Life Science & Technology, Xi'an Jiaotong University, Xi'an 710061, China. zhangjz@nxmc.edu.cn
Jing
Li
L
Ma
Ai-Ling
AL
Wang
Fei
F
Yu
Xin
X
Wang
Yi-Li
YL
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000209:etiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D007120:Immunochemistry; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D048049:Extracellular Signal-Regulated MAP Kinases