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首都医科大学宣武医院
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.
基金:
National Key R&D Program of China [2017YFC1308401]; National Natural Science Foundation of China [82027802, 31671205, 31972911]
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
推荐引用方式(GB/T 7714):
Zhang Ying,Ma Longhui,Yan Yi,et al.cPKC gamma-Modulated Autophagy Contributes to Ischemic Preconditioning-Induced Neuroprotection in Mice with Ischemic Stroke via mTOR-ULK1 Pathway[J].TRANSLATIONAL STROKE RESEARCH.2023,14(5):790-801.doi:10.1007/s12975-022-01094-5.
APA:
Zhang, Ying,Ma, Longhui,Yan, Yi,Zhao, Li,Han, Song...&Ji, Xunming.(2023).cPKC gamma-Modulated Autophagy Contributes to Ischemic Preconditioning-Induced Neuroprotection in Mice with Ischemic Stroke via mTOR-ULK1 Pathway.TRANSLATIONAL STROKE RESEARCH,14,(5)
MLA:
Zhang, Ying,et al."cPKC gamma-Modulated Autophagy Contributes to Ischemic Preconditioning-Induced Neuroprotection in Mice with Ischemic Stroke via mTOR-ULK1 Pathway".TRANSLATIONAL STROKE RESEARCH 14..5(2023):790-801