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Metformin protects PC12 cells and hippocampal neuronsfrom H2 O 2‐induced oxidative damage through activationof AMPK pathway
Xia Zhao1; Zhiwen Zeng1; Uma Gaur1; Jiankang Fang1; Tangming Peng1,2; Shuai Li1; Wenhua Zheng1
2019-02-19
Source PublicationJournal of Cellular Physiology
ISSN0021-9541
Pages16619-16629
AbstractMetformin, a first line anti type 2 diabetes drug, has recently been shown to extend lifespan in various species, and therefore, became the first antiaging drug in clinical trial. Oxidative stress due to excess reactive oxygen species (ROS) is considered to be an important factor in aging and related disease, such as Alzheimer's disease (AD). However, the antioxidative effects of metformin and its underlying mechanisms in neuronal cells is not known. In the present study, we showed that metformin, in clinically relevant concentrations, protected neuronal PC12 cells from H2 O2 -induced cell death. Metformin significantly ameliorated cell death due to H2 O2 insult by restoring abnormal changes in nuclear morphology, intracellular ROS, lactate dehydrogenase, and mitochondrial membrane potential induced by H2 O2 . Hoechst staining assay and flow cytometry analysis revealed that metformin significantly reduced the apoptosis in PC12 cells exposed to H2 O2 . Western blot analysis further demonstrated that metformin stimulated the phosphorylation and activation of AMP-activated protein kinase (AMPK) in PC12 cells, while application of AMPK inhibitor compound C, or knockdown of the expression of AMPK by specific small interfering RNA or short hairpin RNA blocked the protective effect of metformin. Similar results were obtained in primary cultured hippocampal neurons. Taken together, these results indicated that metformin is able to protect neuronal cells from oxidative injury, at least in part, via the activation of AMPK. As metformin is comparatively cheaper with much less side effects in clinic, our findings support its potential to be a drug for prevention and treatment of aging and aging-related diseases.
KeywordAmp-activated Protein Kinase Pc12 Cells Aging Hydrogen Peroxide Metformin
Language英語English
The Source to ArticlePB_Publication
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorWenhua Zheng
Affiliation1.Center of Reproduction, Development &Aging, Faculty of Health Sciences, Universityof Macau, Taipa, Macau, China
2.Department of Neurosurgery, AffiliatedHospital of Southwest Medical University,China
Recommended Citation
GB/T 7714
Xia Zhao,Zhiwen Zeng,Uma Gaur,et al. Metformin protects PC12 cells and hippocampal neuronsfrom H2 O 2‐induced oxidative damage through activationof AMPK pathway[J]. Journal of Cellular Physiology, 2019, 16619-16629.
APA Xia Zhao., Zhiwen Zeng., Uma Gaur., Jiankang Fang., Tangming Peng., Shuai Li., & Wenhua Zheng (2019). Metformin protects PC12 cells and hippocampal neuronsfrom H2 O 2‐induced oxidative damage through activationof AMPK pathway. Journal of Cellular Physiology, 16619-16629.
MLA Xia Zhao,et al."Metformin protects PC12 cells and hippocampal neuronsfrom H2 O 2‐induced oxidative damage through activationof AMPK pathway".Journal of Cellular Physiology (2019):16619-16629.
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