| First Author | Wei H | Year | 2016 |
| Journal | Transl Stroke Res | Volume | 7 |
| Issue | 6 | Pages | 497-511 |
| PubMed ID | 27510769 | Mgi Jnum | J:354835 |
| Mgi Id | MGI:6791840 | Doi | 10.1007/s12975-016-0484-4 |
| Citation | Wei H, et al. (2016) cPKCgamma-Modulated Autophagy in Neurons Alleviates Ischemic Injury in Brain of Mice with Ischemic Stroke Through Akt-mTOR Pathway. Transl Stroke Res 7(6):497-511 |
| abstractText | We have reported that neuron-specific conventional protein kinase C (cPKC)gamma is involved in the development of cerebral hypoxic preconditioning (HPC) and the neuroprotection against ischemic injuries, but its molecular mechanism is unclear. In this study, the adult and postnatal 24 h C57BL/6J wild-type (cPKCgamma(+/+)) and cPKCgamma knockout (cPKCgamma(-/-)) mice were respectively used to establish the models of middle cerebral artery occlusion (MCAO)-induced ischemic stroke in vivo and oxygen-glucose deprivation (OGD)-treated primarily cultured cortical neurons as cell ischemia in vitro. The results showed that cPKCgamma knockout could increase the infarct volume and neuronal cell loss in the peri-infarct region, and enhance the neurological deficits, the impaired coordination, and the reduced muscle strength of mice following 1 h MCAO/1-7 days reperfusion. Meanwhile, cPKCgamma knockout significantly increased the conversion of LC3-I to LC3-II and beclin-1 protein expression, and resulted in more reductions in P-Akt, P-mTOR, and P-S6 phosphorylation levels in the peri-infarct region of mice with ischemic stroke. The autophagy inhibitor BafA1 could enhance or reduce neuronal cell loss in the peri-infarct region of cPKCgamma(+/+) and cPKCgamma(-/-) mice after ischemic stroke. In addition, cPKCgamma knockout and restoration could aggravate or alleviate OGD-induced neuronal ischemic injury in vitro through Akt-mTOR pathway-mediated autophagy. These results suggested that cPKCgamma-modulated neuron-specific autophagy improves the neurological outcome of mice following ischemic stroke through the Akt-mTOR pathway, providing a potential therapeutic target for ischemic stroke. |
