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| Content Provider | Springer Nature Link |
|---|---|
| Author | Yan, Shi Chen, Lin Wei, Xinbing Cheng, Li Kong, Lingjun Liu, Xinyong Zhang, Xiumei Liu, Huiqing |
| Copyright Year | 2014 |
| Abstract | A novel tetramethylpyrazine derivative, CXC195, has been recently shown to protect against cerebral ischemia–reperfusion (I/R) injury. However, the detailed mechanisms underlying the neuroprotection of CXC195 are still unclear. The aim of the present study was to investigate the effects of CXC195 on the phosphorylation of endothelial nitric oxide synthase (eNOS) in response to cerebral I/R and to determine whether phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway might be involved. An in vitro model of oxygen glucose deprivation (OGD) which was performed on primary cultured human aortic endothelial cells (HAECs) and an in vivo middle cerebral artery occlusion (MCAO) model that was performed on Wistar rats were used in this study. CXC195 increased nitric oxide (NO) production and the phosphorylation but not the protein level of eNOS in HAECs subjected to 1 h OGD followed by reperfusion. In addition, CXC195 increased the phosphorylation of Akt; inhibition of PI3K/Akt pathway by a specific inhibitor, wortmannin, suppressed CXC195-induced NO release in HAECs. Consistently, CXC195 treatment significantly restored the phosphorylations of eNOS and Akt in the cortical penumbra of rats subjected to 2 h MCAO followed by reperfusion. Moreover, wortmannin abolished CXC195-induced eNOS phosphorylation and neuroprotection as evidenced by a reversal of the reduction in infarct volume and neurobehavioral outcomes. In conclusion, CXC195 induced phosphorylation of eNOS by activation of PI3K/Akt signaling under pathological cerebral I/R conditions, which provided a novel explanation for the neuroprotective effect of CXC195. |
| Starting Page | 446 |
| Ending Page | 454 |
| Page Count | 9 |
| File Format | |
| ISSN | 03643190 |
| Journal | Neurochemical Research |
| Volume Number | 40 |
| Issue Number | 3 |
| e-ISSN | 15736903 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2014-11-27 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Tetramethylpyrazine derivative CXC195 Cerebral ischemia–reperfusion Endothelial nitric oxide synthase Akt Phosphorylation PI3K Neurosciences Neurochemistry Biochemistry Cell Biology Neurology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Biochemistry Cellular and Molecular Neuroscience |
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