title: cPKCγ-Modulated Autophagy in Neurons Alleviates Ischemic Injury in Brain of Mice with Ischemic Stroke Through Akt-mTOR Pathway.
abstract: We have reported that neuron-specific conventional protein kinase C (cPKC)γ 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 (cPKCγ+/+) and cPKCγ knockout (cPKCγ-/-) 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 cPKCγ 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, cPKCγ 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 cPKCγ+/+and cPKCγ-/-mice after ischemic stroke. In addition, cPKCγ knockout and restoration could aggravate or alleviate OGD-induced neuronal ischemic injury in vitro through Akt-mTOR pathway-mediated autophagy. These results suggested that cPKCγ-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.
authors: Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing, 100069, People's Republic of China.
authors: Haiping
authors: H
authors: Wei
authors: Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing, 100069, People's Republic of China.
authors: Yun
authors: Y
authors: Li
authors: Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing, 100069, People's Republic of China.
authors: Song
authors: S
authors: Han
authors: Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing, 100069, People's Republic of China.
authors: Shuiqiao
authors: S
authors: Liu
authors: Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing, 100069, People's Republic of China.
authors: Nan
authors: N
authors: Zhang
authors: Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing, 100069, People's Republic of China.
authors: Li
authors: L
authors: Zhao
authors: Department of Neurology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China. shujuanli@ccmu.edu.cn.
authors: Shujuan
authors: S
authors: Li
authors: Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing, 100069, People's Republic of China. junfali@ccmu.edu.cn.
authors: Junfa
authors: J
authors: Li
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002544:Cerebral Infarction / Q000209:etiology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D005947:Glucose / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009422:Nervous System Diseases / Q000209:etiology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D020521:Stroke / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors
chemical_list: D058570:TOR Serine-Threonine Kinases; D011493:Protein Kinase C; D005947:Glucose
keywords: Akt-mTOR pathway; Autophagy; Beclin 1; Ischemic stroke; Protein kinase C (PKC)