title: Metformin-induced protection against oxidative stress is associated with AKT/mTOR restoration in PC12 cells.
abstract: OBJECTIVE
  Reactive oxygen species have been recognized to impair cell function through suppressing Akt the well-known 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.
  
  
  METHODS
  In the current study using H2O2 induced injury in PC12 cells; we first examined metformin 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 post-transcriptional changes. The proportions of phosphorylated to non-phosphorylated constituents of PI3K/Akt/mTOR/S6K were determined to address their activation upon metformin treatment.
  
  
  RESULTS
  According to cells morphology and MTT data metformin led to significant protection against H2O2 induced injury in 0.1 and 0.5mM 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.
  
  
  CONCLUSIONS
  Taken together our experimentation supports the hypothesis that Akt/mTOR/S6K cascade may contribute to metformin 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.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Khallaghi
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Safarian
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Nasoohi
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Abolhassan
authors.initials: A
authors.lastname: Ahmadiani
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: l.dargahi@sbmu.ac.ir.
authors.forename: Leila
authors.initials: L
authors.lastname: Dargahi
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008687:Metformin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D016716:PC12 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D008687:Metformin; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Akt; Metformin; Oxidative stress; mTOR