MicroRNA-30b-mediated regulation of catalase expression in human ARPE-19 cells

PLoS One. 2012;7(8):e42542. doi: 10.1371/journal.pone.0042542. Epub 2012 Aug 6.

Abstract

Background: Oxidative injury to retinal pigment epithelium (RPE) and retinal photoreceptors has been linked to a number of retinal diseases, including age-related macular degeneration (AMD). Reactive oxygen species (ROS)-mediated gene expression has been extensively studied at transcriptional levels. Also, the post-transcriptional control of gene expression at the level of translational regulation has been recently reported. However, the microRNA (miRNA/miR)-mediated post-transcriptional regulation in human RPE cells has not been thoroughly looked at. Increasing evidence points to a potential role of miRNAs in diverse physiological processes.

Methodology/principal findings: We demonstrated for the first time in a human retinal pigment epithelial cell line (ARPE-19) that the post-transcriptional control of gene expression via miRNA modulation regulates human catalase, an important and potent component of cell's antioxidant defensive network, which detoxifies hydrogen peroxide (H(2)O(2)) radicals. Exposure to several stress-inducing agents including H(2)O(2) has been reported to alter miRNA expression profile. Here, we demonstrated that a sublethal dose of H(2)O(2) (200 µM) up-regulated the expression of miR-30b, a member of the miR-30 family, which inhibited the expression of endogenous catalase both at the transcript and protein levels. However, antisense (antagomirs) of miR-30b was not only found to suppress the miR-30b mimics-mediated inhibitions, but also to dramatically increase the expression of catalase even under an oxidant environment.

Conclusions/significance: We propose that a microRNA antisense approach could enhance cytoprotective mechanisms against oxidative stress by increasing the antioxidant defense system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Base Sequence
  • Catalase / antagonists & inhibitors
  • Catalase / genetics*
  • Catalase / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Computational Biology
  • Cytoprotection / drug effects
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Humans
  • Hydrogen Peroxide / pharmacology
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Oligonucleotides / pharmacology
  • Oxidative Stress / drug effects
  • Protein Binding / drug effects
  • Protein Carbonylation / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Retinal Pigment Epithelium / cytology*
  • Retinal Pigment Epithelium / drug effects
  • Retinal Pigment Epithelium / enzymology*

Substances

  • 3' Untranslated Regions
  • MIRN30b microRNA, human
  • MicroRNAs
  • Oligonucleotides
  • RNA, Messenger
  • Hydrogen Peroxide
  • CAT protein, human
  • Catalase

Associated data

  • RefSeq/NM_000194
  • RefSeq/NM_001752