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cPKC gamma-Modulated Autophagy Contributes to Ischemic Preconditioning-Induced Neuroprotection in Mice with Ischemic Stroke via mTOR-ULK1 Pathway

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机构: [1]Capital Med Univ, Dept Neurobiol, 10 You An Men Wai Xi Tou Tiao, Beijing 100069, Peoples R China [2]Beijing Key Lab Hypoxia Conditioning Translat Med, Beijing 100053, Peoples R China [3]Capital Med Univ, Beijing Inst Brain Disorders, Beijing 100069, Peoples R China [4]Univ S Florida, Dept Neurosurg & Brain Repair, Coll Med, Tampa, FL 33612 USA [5]Capital Med Univ, Xuanwu Hosp, Dept Neurosurg, Beijing 100053, Peoples R China
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关键词: Conventional protein kinase C (cPKC)gamma Ischemic preconditioning (IPC) Ischemic stroke Autophagy mTOR-ULK1 signaling pathway

摘要:
Neuron-specific conventional protein kinase C (cPKC)gamma mediates cerebral hypoxic preconditioning (HPC). In parallel, autophagy plays a prosurvival role in ischemic preconditioning (IPC) against ischemic stroke. However, the effect of cPKC gamma on autophagy in IPC still remains to be addressed. In this study, adult and postnatal 1-day-old C57BL/6 J wild-type (cPKC gamma(+/+)) and knockout (cPKC gamma(-/-)) mice were used to establish in vivo and in vitro IPC models. The results showed that IPC pretreatment alleviated neuronal damage caused by lethal ischemia, which could be suppressed by autophagy inhibitor 3-MA or bafilomycin A1. Meanwhile, cPKC gamma knockout blocked IPC-induced neuroprotection, accompanied by significant increase of LC3-I to LC3-II conversion and Beclin 1 protein level, and a significant decrease in p62 protein level. Immunofluorescent staining results showed a decrease of LC3 puncta numbers in IPC-treated cPKC gamma(+/+) neurons with fatal ischemia, which was reversed in cPKC gamma(-/-) neurons. In addition, cPKC gamma-modulated phosphorylation of mTOR at Ser 2448 and ULK1 at Ser 555, rather than p-Thr-172 AMPK, was detected in IPC-pretreated neurons upon lethal ischemic exposure. The present data demonstrated that cPKC gamma-modulated autophagy via the mTOR-ULK1 pathway likely modulated IPC-induced neuroprotection.

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基金编号: 2017YFC1308401 82027802 31671205 31972911

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出版当年[2022]版:
大类 | 1 区 医学
小类 | 1 区 临床神经病学 2 区 神经科学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 临床神经病学 2 区 神经科学
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出版当年[2021]版:
Q1 CLINICAL NEUROLOGY Q1 NEUROSCIENCES
最新[2023]版:
Q1 CLINICAL NEUROLOGY Q2 NEUROSCIENCES

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者机构: [1]Capital Med Univ, Dept Neurobiol, 10 You An Men Wai Xi Tou Tiao, Beijing 100069, Peoples R China [2]Beijing Key Lab Hypoxia Conditioning Translat Med, Beijing 100053, Peoples R China [3]Capital Med Univ, Beijing Inst Brain Disorders, Beijing 100069, Peoples R China
通讯作者:
通讯机构: [1]Capital Med Univ, Dept Neurobiol, 10 You An Men Wai Xi Tou Tiao, Beijing 100069, Peoples R China [2]Beijing Key Lab Hypoxia Conditioning Translat Med, Beijing 100053, Peoples R China [3]Capital Med Univ, Beijing Inst Brain Disorders, Beijing 100069, Peoples R China [5]Capital Med Univ, Xuanwu Hosp, Dept Neurosurg, Beijing 100053, Peoples R China
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