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Metformin protects PC12 cells and hippocampal neurons from H 2 O 2 ‐induced oxidative damage through activation of AMPK pathway
Author(s) -
Zhao Xia,
Zeng Zhiwen,
Gaur Uma,
Fang Jiankang,
Peng Tangming,
Li Shuai,
Zheng Wenhua
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28337
Subject(s) - metformin , ampk , oxidative stress , amp activated protein kinase , reactive oxygen species , microbiology and biotechnology , neuroprotection , mitochondrion , apoptosis , pharmacology , protein kinase a , intracellular , programmed cell death , chemistry , biology , endocrinology , kinase , diabetes mellitus , biochemistry
Metformin, 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 H 2 O 2 ‐induced cell death. Metformin signicantly ameliorated cell death due to H 2 O 2 insult by restoring abnormal changes in nuclear morphology, intracellular ROS, lactate dehydrogenase, and mitochondrial membrane potential induced by H 2 O 2 . Hoechst staining assay and flow cytometry analysis revealed that metformin significantly reduced the apoptosis in PC12 cells exposed to H 2 O 2 . 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.