Metformin Protects against Oxidative Stress Injury Induced by IschemiaReperfusion via Regulation of the lncRNA-H19miR-148a-3pRock2 Axis
Joint Authors
Zhang, Hao
Zeng, Jing
Zhu, Long
Liu, Jing
Zhu, Tao
Xie, Zhaohui
Sun, Xiaoou
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-18, 18 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-12-17
Country of Publication
Egypt
No. of Pages
18
Main Subjects
Abstract EN
Previous studies have shown that metformin not only is a hypoglycemic agent but also has neuroprotective effects.
However, the mechanism of action of metformin in ischemic stroke is unclear.
Oxidative stress is an important factor in the pathogenesis of cerebral ischemia-reperfusion injury.
It has been reported that metformin is associated with stroke risk in the clinical population.
This study is aimed at investigating the effect and mechanism of metformin in an experimental model of oxidative stress induced by ischemia/reperfusion (I/R) in vivo and oxygen glucose deprivation/reperfusion (OGD/R) in vitro.
Metformin (100, 200, and 300 mg/kg) was administered intraperitoneally immediately after induction of cerebral ischemia.
The indicators of oxidative stress selected were antioxidant enzyme activities of catalase, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidation enzyme (GSHPx).
First, we demonstrated that metformin can significantly alleviate acute and chronic cerebral I/R injury and it has a strong regulatory effect on stroke-induced oxidative stress.
It can reduce the elevated activities of MDA and NO and increase the levels of GSHPx and SOD in the cerebrum of mice and N2a cells exposed to I/R.
Furthermore, real-time PCR and western blot were used to detect the expression of long noncoding RNA H19 (lncRNA-H19), microRNA-148a-3p (miR-148a-3p), and Rho-associated protein kinase 2 (Rock2).
The direct interaction of lncRNA-H19, miR-148a-3p, and Rock2 was tested using a dual luciferase reporter assay.
lncRNA-H19 altered OGD/R-induced oxidative stress by modulating miR-148a-3p to increase Rock2 expression.
The expression of lncRNA-H19 and Rock2 could be downregulated with metformin in vivo and in vitro.
In conclusion, our study confirmed that metformin exerts neuroprotective effects by regulating ischemic stroke-induced oxidative stress injury via the lncRNA-H19/miR-148a-3p/Rock2 axis.
These results provide new evidence that metformin may represent a potential treatment for stroke-related brain injury.
American Psychological Association (APA)
Zeng, Jing& Zhu, Long& Liu, Jing& Zhu, Tao& Xie, Zhaohui& Sun, Xiaoou…[et al.]. 2019. Metformin Protects against Oxidative Stress Injury Induced by IschemiaReperfusion via Regulation of the lncRNA-H19miR-148a-3pRock2 Axis. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-18.
https://search.emarefa.net/detail/BIM-1205930
Modern Language Association (MLA)
Zeng, Jing…[et al.]. Metformin Protects against Oxidative Stress Injury Induced by IschemiaReperfusion via Regulation of the lncRNA-H19miR-148a-3pRock2 Axis. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-18.
https://search.emarefa.net/detail/BIM-1205930
American Medical Association (AMA)
Zeng, Jing& Zhu, Long& Liu, Jing& Zhu, Tao& Xie, Zhaohui& Sun, Xiaoou…[et al.]. Metformin Protects against Oxidative Stress Injury Induced by IschemiaReperfusion via Regulation of the lncRNA-H19miR-148a-3pRock2 Axis. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-18.
https://search.emarefa.net/detail/BIM-1205930
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205930