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Orexin-A protects against cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through OX1R-mediated MAPK/ERK/mTOR pathway
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Xu, Dandan, Kong, Tingting, Zhang, Shengnan, Cheng, Baohua, Chen, Jing and Wang, Chunmei (2021) Orexin-A protects against cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through OX1R-mediated MAPK/ERK/mTOR pathway. Cellular Signalling, 79 . 109839. doi:10.1016/j.cellsig.2020.109839
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Official URL: http://dx.doi.org/10.1016/j.cellsig.2020.109839
Abstract
Orexin A (OXA) is a neuroprotective peptide that exerts protective effects on multiple physiological and pathological processes. Activation of autophagy is linked to the occurrence of cerebral ischemia–reperfusion injury (CIRI); however, its function remains incompletely understood. In this study, OXA was sought to exert its neuroprotective role by regulating autophagy in oxygen and glucose deprivation and reoxygenation (OGD/R) model and middle cerebral artery occlusion (MCAO) model of rats, and to elucidate the underlying molecular mechanisms. Acridine orange (AO) staining was used to evaluate autophagic vacuoles. Cell viability was measured by CCK8. The levels of p-ERK1/2, t-ERK1/2, p-mTOR, LC3B, Beclin 1, and p62 were evaluated by western blotting. Apoptosis rate was detected by Hoechst 33342 staining and Terminal deoxynucleotidyltransferase–mediated dUTP nick-end labeling (TUNEL). OXA treatment alleviated neuronal apoptosis and significantly inhibited autophagy activity. Mechanistically, OXA exerted its neuroprotective effects in vivo and in vitro by suppressing over-activated autophagy by modulating OX1R-mediated MAPK/ERK/mTOR pathway. The results of this study elucidate the roles of autophagy in CIRI and the mechanisms underlying the neuroprotective action of OXA. Our findings could facilitate the development of novel therapeutics for ischemic stroke.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Orexins , Cell death , Cerebral ischemia , Oxygen -- Physiological transport , Neuroprotective agents | ||||||||
| Journal or Publication Title: | Cellular Signalling | ||||||||
| Publisher: | Elsevier | ||||||||
| ISSN: | 0898-6568 | ||||||||
| Official Date: | March 2021 | ||||||||
| Dates: |
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| Volume: | 79 | ||||||||
| Article Number: | 109839 | ||||||||
| DOI: | 10.1016/j.cellsig.2020.109839 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||
| RIOXX Funder/Project Grant: |
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