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

• Published in: PloS one 2012-08, Vol.7 (8), p.e42542
• Main Authors: Haque, Rashidul, Chun, Eugene, Howell, Jennifer C, Sengupta, Trisha, Chen, Dan, Kim, Hana
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Age; Alzheimer's disease; Antioxidants; Antisense RNA; Base Sequence; Biology; Catalase; Catalase - antagonists & inhibitors; Catalase - genetics; Catalase - metabolism; Cell Line; Cell Survival - drug effects; Computational Biology; Cytoprotection - drug effects; Deoxyribonucleic acid; Diabetes; Diabetic retinopathy; DNA; Epithelium; Gene expression; Gene Expression Regulation, Enzymologic - drug effects; Gene regulation; Genes; Genetic aspects; Humans; Hydrogen; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Macaca mulatta; Macular degeneration; Medicine; MicroRNA; MicroRNAs; MicroRNAs - metabolism; miRNA; Mitochondria; Molecular Sequence Data; Oligonucleotides - pharmacology; Oxidative stress; Oxidative Stress - drug effects; Oxidizing agents; Oxygen; Pan troglodytes; Photoreceptors; Physiological aspects; Post-transcription; Protein Binding - drug effects; Protein Carbonylation - drug effects; Proteins; Reactive oxygen species; Reproducibility of Results; Retina; Retinal pigment epithelium; Retinal Pigment Epithelium - cytology; Retinal Pigment Epithelium - drug effects; Retinal Pigment Epithelium - enzymology; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Sublethal dosage; Transcription (Genetics)
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0042542

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