LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress.
Animals
Autophagy
/ physiology
Brain Ischemia
/ metabolism
Cell Hypoxia
/ physiology
Cell Line
Forkhead Box Protein O3
/ antagonists & inhibitors
Hippocampus
/ metabolism
Mice
Oxidative Stress
/ physiology
RNA, Long Noncoding
/ metabolism
Reperfusion Injury
/ metabolism
Signal Transduction
/ physiology
Sirtuin 1
/ antagonists & inhibitors
Ischemia/reperfusion injury
LncRNA
SIRT1/FOXO3a
apoptosis
autophagy
oxidative stress
Journal
Current neurovascular research
ISSN: 1875-5739
Titre abrégé: Curr Neurovasc Res
Pays: United Arab Emirates
ID NLM: 101208439
Informations de publication
Date de publication:
2020
2020
Historique:
received:
01
04
2020
revised:
14
04
2020
accepted:
22
04
2020
pubmed:
29
7
2020
medline:
1
10
2021
entrez:
29
7
2020
Statut:
ppublish
Résumé
Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.
Sections du résumé
BACKGROUND
Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury.
METHODS
This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model.
RESULTS
Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA.
CONCLUSION
In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.
Identifiants
pubmed: 32718291
pii: CNR-EPUB-108503
doi: 10.2174/1567202617666200727142019
doi:
Substances chimiques
Forkhead Box Protein O3
0
FoxO3 protein, mouse
0
RNA, Long Noncoding
0
SNHG12 long non-coding RNA, human
0
Sirt1 protein, mouse
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
394-401Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.