MicroRNA-144 modulates oxidative stress tolerance in SH-SY5Y cells by regulating nuclear factor erythroid 2-related factor 2-glutathione axis

Neurosci Lett. 2017 Aug 10:655:21-27. doi: 10.1016/j.neulet.2017.06.045. Epub 2017 Jun 27.

Abstract

Genome-wide analysis of miRNA expression has revealed increased levels of miR-144 in the brains of Alzheimer's disease (AD) patients. Nuclear factor erythroid 2-related factor 2 (NRF2), a potential target of miR-144, is a central regulator of antioxidant response, and plays an important role in glutathione (GSH) biosynthesis and recycling. In this study, miR-144 mimic was used to over express miR-144. Aβ (1-42) was used to induce oxidative stress in SH-SY5Y cells. Cell viability and intracellular reactive oxygen species (ROS) were assessed to identify the effects of miR-144 on oxidative stress status. GSH and glutathion peroxidase (GPX) activities were detected to reveal the effect of miR-144 on GSH accumulation. To understand the effects of miR-144 on GSH biosynthesis and recycling, intracellular GPX1, glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), glutathione reductase (GR), and NRF2 expression were detected by western blot and Real-time PCR. In oxidative stress conditions, miR-144 increased the intracellular accumulation of ROS, reduced cell viability, reduced the activities of GSH and antioxidant enzymes, GPX1, and decreased the expression of GCLC, GCLM, GR and NRF2. In conclusion, miR-144 modulates oxidative stress tolerance by regulating NRF2 expression and GSH generation, which may contribute to the pathogenesis of AD.

Keywords: Alzheimer’s disease; Nuclear factor erythroid 2-related factor 2; Oxidative stress; microRNA-144.

MeSH terms

  • Amyloid beta-Peptides / toxicity
  • Cell Line, Tumor
  • Cell Survival
  • Glutathione / metabolism*
  • Glutathione Peroxidase / metabolism
  • Humans
  • MicroRNAs / metabolism*
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress*
  • Peptide Fragments / toxicity
  • Reactive Oxygen Species / metabolism

Substances

  • Amyloid beta-Peptides
  • MIRN144 microRNA, human
  • MicroRNAs
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Peptide Fragments
  • Reactive Oxygen Species
  • amyloid beta-protein (1-42)
  • Glutathione Peroxidase
  • Glutathione