Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Orexin-A protects against oxygen-glucose deprivation/reoxygenation-induced cell damage by inhibiting endoplasmic reticulum stress-mediated apoptosis via the Gi and PI3K signaling pathways

Tools
- Tools
+ Tools

Kong, Tingting, Qiu, Kaixin, Liu, Minghui, Cheng, Baohua, Pan, Yanyou, Yang, Chunqing, Chen, Jing and Wang, Chunmei (2019) Orexin-A protects against oxygen-glucose deprivation/reoxygenation-induced cell damage by inhibiting endoplasmic reticulum stress-mediated apoptosis via the Gi and PI3K signaling pathways. Cellular Signalling, 62 . 109348. doi:10.1016/j.cellsig.2019.109348

[img]
Preview
PDF
WRAP-orexin-A-protects-against-oxygen-glucose-deprivation-reoxygenation-induced-cell-damage-Chen-2019.pdf - Accepted Version - Requires a PDF viewer.
Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0.

Download (951Kb) | Preview
Official URL: http://dx.doi.org/10.1016/j.cellsig.2019.109348

Request Changes to record.

Abstract

The neuropeptide orexin-A (OXA) has a neuroprotective effect, acting as an anti-apoptotic factor in response to multiple stimuli. Apoptosis induced by endoplasmic reticulum stress (ERS) underlies oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell damage, an in vitro model of ischemia/reperfusion injury. However, that OXA inhibits ERS-induced apoptosis in the OGD/R model has not been reported. In the present study, we investigated the neuroprotective effect of OXA (0.1 μM) on OGD/R-induced damage in the human neuroblastoma cell line SH-SY5Y. After OXA treatment following 4 h oxygen-glucose deprivation (OGD) and then 4 h reoxygenation (R), cell morphology, viability, and apoptosis were analyzed by histology, Cell Counting Kit-8 assay, and flow cytometry, respectively. Western blotting was used to measure expression levels of ERS- and apoptosis-related proteins. To determine signaling pathways involved in OXA-mediated neuroprotection, the Gi pathway inhibitor pertussis toxin (PTX; 100 ng/mL) and PI3K inhibitor LY294002 (LY; 10 μM) were added. In addition, in order to prove the specificity of these characteristics, the OXA antagonist Suvorexant (DORA; Ki of 0.55 nM and 0.35 nM for OX1R and OX2R) was used for intervention. Our results showed that OGD/R induced cell damage, manifested as morphological changes and a significant decrease in viability. Furthermore, Western blotting detected an increase in ERS-related proteins GRP78, p-IRE1α, p-JNK, and Cleaved caspase-12, as well as apoptosis-related proteins Cleaved caspase-3 and Bax, and a decrease in the anti-apoptosis factor Bcl-2. OXA intervention alleviated the degree of cellular damage, and protein expression was also reversed. In addition, the protective effect of OXA was reduced by adding PTX and LY. Meanwhile, after the use of DORA, changes in the expression of related proteins were detected, and it was found that the protective effect of OXA was weakened. Collectively, our results indicate that OXA has a neuroprotective effect on OGD/R-induced cell damage by inhibiting ERS-induced apoptosis through the combined action of Gi and PI3K signaling pathways. These findings help to clarify the mechanism underlying the neuroprotective action of OXA, which should aid the development of further candidate drugs, and provide a new therapeutic direction for the treatment of ischemic stroke.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
Q Science > QP Physiology
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
Library of Congress Subject Headings (LCSH): Orexins , Neuroprotective agents , Apoptosis, Endoplasmic reticulum, Insulin resistance
Journal or Publication Title: Cellular Signalling
Publisher: Elsevier
ISSN: 0898-6568
Official Date: October 2019
Dates:
DateEvent
October 2019Published
21 June 2019Available
20 June 2019Accepted
Volume: 62
Article Number: 109348
DOI: 10.1016/j.cellsig.2019.109348
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
81501018[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
81671276[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
81870948 [NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
1271243[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
ZR2018MC005Natural Science Foundation of Shandong Provincehttp://dx.doi.org/10.13039/501100007129
JY2017KJ034Jining Medical Universityhttp://dx.doi.org/10.13039/501100008853
JYFC2018JS008Jining Medical Universityhttp://dx.doi.org/10.13039/501100008853

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us