Evaluation of lovastatin effects on expression of anti-apoptotic Nrf2 and PGC-1α genes in neural stem cells treated with hydrogen peroxide

Mol Neurobiol. 2014 Jun;49(3):1364-72. doi: 10.1007/s12035-013-8613-5. Epub 2014 Jan 5.

Abstract

Reactive oxygen species and oxidative stress are associated with various cell processes, including cell survival and apoptosis. Oxidative stress has been implicated in the pathogenesis of several neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS). In the present study, we evaluated the effects of lovastatin chemoprotection against hydrogen peroxide-induced oxidative stress in bone marrow stromal cell-derived neural stem cells (BMSC-derived NSCs) and whether it has protective effects. BMSC-derived NSCs were pretreated with different doses of lovastatin for 48 h and then exposed to 125 μM H2O2 for 30 min. Using MTT, TUNEL assay, and real-time RT-PCR, we evaluated the effects of lovastatin on cell survival, apoptosis, and PGC-1α and Nrf2 expression rates in pretreated BMSC-derived NSCs compared to control groups. Results showed that apoptosis rate in the lovastatin-pretreated BMSC-derived NSCs was significantly decreased compared to the control group. Our findings suggest that lovastatin protects NSCs against oxidative stress-induced cell death, and therefore, it may be used to promote the survival rate of NSCs and can be a candidate for treatment of oxidative stress-mediated neurological diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cells, Cultured
  • Drug Evaluation, Preclinical / methods
  • Gene Expression Regulation
  • Hydrogen Peroxide / toxicity*
  • Lovastatin / pharmacology*
  • NF-E2-Related Factor 2 / biosynthesis*
  • NF-E2-Related Factor 2 / genetics
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Rats
  • Rats, Wistar
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • Transcription Factors
  • Lovastatin
  • Hydrogen Peroxide