Protective Effect of Metformin against Hydrogen Peroxide-Induced Oxidative Damage in Human Retinal Pigment Epithelial (RPE) Cells by Enhancing Autophagy through Activation of AMPK Pathway
Joint Authors
Zhao, Xia
Liu, Linlin
Jiang, Yizhou
Silva, Marta
Zhen, Xuechu
Zheng, Wenhua
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-07-25
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Age-related macular degeneration (AMD) is a leading cause of blindness with limited effective treatment.
Although the pathogenesis of this disease is complex and not fully understood, the oxidative damage caused by excessive reactive oxygen species (ROS) in retinal pigment epithelium (RPE) has been considered as a major cause.
Autophagy is essential for the degradation of cellular components damaged by ROS, and its dysregulation has been implicated in AMD pathogenesis.
Therefore, strategies aiming to boost autophagy could be effective in protecting RPE cells from oxidative damage.
Metformin is the first-line anti-type 2 diabetes drug and has been reported to stimulate autophagy in many tissues.
We therefore hypothesized that metformin may be able to protect RPE cells against H2O2-induced oxidative damage by autophagy activation.
In the present study, we found that metformin attenuated H2O2-induced cell viability loss, apoptosis, elevated ROS levels, and the collapse of the mitochondria membrane potential in D407 cells.
Autophagy was stimulated by metformin, and inhibition of autophagy by 3-methyladenine (3-MA) and chloroquine (CQ) or knockdown of Beclin1 and LC3B blocked the protective effects of metformin.
In addition, we showed that metformin could activate the AMPK pathway, whereas both pharmacological and genetic inhibitions of AMPK blocked the autophagy-stimulating and protective effects of metformin.
Metformin conferred a similar protection against H2O2-induced oxidative damage in primary cultured human RPE cells.
Taken together, these results demonstrate that metformin could protect RPE cells from H2O2-induced oxidative damage by stimulating autophagy via the activation of the AMPK pathway, supporting its potential use in the prevention and treatment of AMD.
American Psychological Association (APA)
Zhao, Xia& Liu, Linlin& Jiang, Yizhou& Silva, Marta& Zhen, Xuechu& Zheng, Wenhua. 2020. Protective Effect of Metformin against Hydrogen Peroxide-Induced Oxidative Damage in Human Retinal Pigment Epithelial (RPE) Cells by Enhancing Autophagy through Activation of AMPK Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1203982
Modern Language Association (MLA)
Zhao, Xia…[et al.]. Protective Effect of Metformin against Hydrogen Peroxide-Induced Oxidative Damage in Human Retinal Pigment Epithelial (RPE) Cells by Enhancing Autophagy through Activation of AMPK Pathway. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1203982
American Medical Association (AMA)
Zhao, Xia& Liu, Linlin& Jiang, Yizhou& Silva, Marta& Zhen, Xuechu& Zheng, Wenhua. Protective Effect of Metformin against Hydrogen Peroxide-Induced Oxidative Damage in Human Retinal Pigment Epithelial (RPE) Cells by Enhancing Autophagy through Activation of AMPK Pathway. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1203982
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203982