Metformin-induced protection against oxidative stress is associated with AKT/mTOR restoration in PC12 cells

Aims: Reactive oxygen species have been recognized to impair cell function through suppressing Akt the wellknown pro-survival molecule. Pile of concrete evidence imply metformin as an Insulin sensitizer may enhance Akt/mTOR activity however the significance of Akt/mTOR recruitment has not yet been revealed in metformin induced neuroprotection against oxidative stress. Main methods: In the current study using H2O2 induced injury in PC12 cells; we first examinedmetformin impact on cell death by MTT assay and visual assessment. Metformin pretreated cells were then subjected to immunoblotting as well as real time PCR to find PI3K, Akt, mTOR and S6K concurrent transcriptional and posttranscriptional changes. The proportions of phosphorylated to non-phosphorylated constituents of PI3K/Akt/ mTOR/S6K were determined to address their activation upon metformin treatment. Key findings: According to cells morphology and MTT data metformin led to significant protection against H2O2 induced injury in 0.1 and 0.5 mM concentrations. Metformin induced protection concurred with elevated PI3K/Akt/mTOR/S6K activity as well as enhanced GSH levels. These changes paralleled with a profound decline in the corresponding transcripts as determined by real time PCR. Significance: Taken together our experimentation supports the hypothesis that Akt/mTOR/S6K cascademay contribute tometformin alleviating effect. The present work while highlighting metformin anti-oxidant characteristics, concludes that Akt/mTOR signaling might be central to the drug's alleviating effects. (C) 2016 Elsevier Inc. All rights reserved.