title: MicroRNA-30b-mediated regulation of catalase expression in human ARPE-19 cells.
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.
  
  
  RESULTS
  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
  We propose that a microRNA antisense approach could enhance cytoprotective mechanisms against oxidative stress by increasing the antioxidant defense system.
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States of America. rhaque@emory.edu
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.forename: Eugene
authors.initials: E
authors.lastname: Chun
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Howell
authors.forename: Trisha
authors.initials: T
authors.lastname: Sengupta
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Hana
authors.initials: H
authors.lastname: Kim
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D002374:Catalase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D019610:Cytoprotection / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*
chemical_list: D020413:3' Untranslated Regions; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; C577219:CAT protein, human; D002374:Catalase