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Activation of AMPK pathway is involved in the protection of Metformin on PC12 cells and hippocampal neurons against H2O2-induced oxidative damage
Zheng, W.
2018-12-01
Conference Name第三届表观遗传与生物医药研究国际会议
Source Publication第三届表观遗传与生物医药研究国际会议
Conference Date2018-12
Conference Place-
Abstract

Oxidative stress-induced cell damage is considered to be an important factor in aging and neurodegenerative diseases such as Alzheimer's disease (AD). Metformin, a clinically most commonly used anti-type 2 diabetes drug, has recently been shown to extend the lifespan of various species and is therefore the preferred anti-aging drug in clinical trials. However, the antioxidant effects of metformin and its underlying mechanisms in neuronal cells are unclear. Excessive reactive oxygen species (ROS) can cause oxidative stress, and excess H2O2 is one of the main sources of reactive oxygen species. In the present study, we found that metformin protects neuronal PC12 cells from H2O2-induced cell death at clinically relevant concentrations. H2O2 causes abnormal changes in intracellular ROS, lactate dehydrogenase and mitochondrial membrane potential in PC12 cells, while metformin treatment significantly improved those changes caused by H2O2 injury. Hoechst staining analysis and flow cytometry analysis showed that metformin significantly reduced apoptosis of PC12 cells exposed to H2O2. Western blot analysis further demonstrated that metformin stimulated the phosphorylation and activation of AMPK in PC12 cells, and the protective effect of metformin was blocked by knockdown AMPK using inhibitor compound C and knock down plasmid. Similar results were obtained in primary cultured hippocampal neurons. Taken together, these results indicate that metformin is capable of at least partially protecting neuronal cells from oxidative damage by activation of AMPK. Because metformin is relatively inexpensive and has fewer clinical side effects, our findings support its potential as a drug for the prevention and treatment of aging and aging-related diseases.

KeywordAging Metformin Pc12 Cells Hydrogen Peroxide Amp-activated Protein Kinase
Language英語English
The Source to ArticlePB_Publication
Document TypeConference paper
CollectionDEPARTMENT OF PHARMACEUTICAL SCIENCES
Faculty of Health Sciences
Corresponding AuthorZheng, W.
Recommended Citation
GB/T 7714
Zheng, W.. Activation of AMPK pathway is involved in the protection of Metformin on PC12 cells and hippocampal neurons against H2O2-induced oxidative damage[C],2018.
APA Zheng, W..(2018).Activation of AMPK pathway is involved in the protection of Metformin on PC12 cells and hippocampal neurons against H2O2-induced oxidative damage.第三届表观遗传与生物医药研究国际会议.
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