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

Authors :
Zhang Y
Ma L
Yan Y
Zhao L
Han S
Wu D
Borlongan CV
Li J
Ji X
Source :
Translational stroke research [Transl Stroke Res] 2023 Oct; Vol. 14 (5), pp. 790-801. Date of Electronic Publication: 2022 Oct 10.
Publication Year :
2023

Abstract

Neuron-specific conventional protein kinase C (cPKC)γ mediates cerebral hypoxic preconditioning (HPC). In parallel, autophagy plays a prosurvival role in ischemic preconditioning (IPC) against ischemic stroke. However, the effect of cPKCγ on autophagy in IPC still remains to be addressed. In this study, adult and postnatal 1-day-old C57BL/6 J wild-type (cPKCγ <superscript>+/+</superscript> ) and knockout (cPKCγ <superscript>-/-</superscript> ) 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, cPKCγ 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 cPKCγ <superscript>+/+</superscript> neurons with fatal ischemia, which was reversed in cPKCγ <superscript>-/-</superscript> neurons. In addition, cPKCγ-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 cPKCγ-modulated autophagy via the mTOR-ULK1 pathway likely modulated IPC-induced neuroprotection.<br /> (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Details

Language :
English
ISSN :
1868-601X
Volume :
14
Issue :
5
Database :
MEDLINE
Journal :
Translational stroke research
Publication Type :
Academic Journal
Accession number :
36214939
Full Text :
https://doi.org/10.1007/s12975-022-01094-5