Methionine sulfoxide reductase B2 is highly expressed in the retina and protects retinal pigmented epithelium cells from oxidative damage.
Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial enzyme that converts methionine sulfoxide (R) enantiomer back to methionine. This enzyme is suspected of functioning to protect mitochondrial proteins from oxidative damage. In this study we report that the retina is one of the human tissues with highest levels of MSRB2 mRNA expression. Other tissues with high expression were heart, kidney and skeletal muscle. Overexpression of an MSRB2-GFP fusion protein increased the MSR enzymatic activity three-fold in stably transfected cultured RPE cells. This overexpression augmented the resistance of these cells to the toxicity induced by 7-ketocholesterol, tert-butyl hydroperoxide and all-trans retinoic acid. By contrast, knockdown of MSRB2 by a miRNA in stably transfected cells did not convey increased sensitivity to the oxidative stress. In the monkey retina MSRB2 localized to the ganglion cell layer (GLC), the outer plexiform layer (OPL) and the retinal pigment epithelium (RPE). MSRB2 expression is most pronounced in the OPL of the macula and foveal regions suggesting an association with the cone synaptic mitochondria. Our data suggests that MSRB2 plays an important function in protecting cones from multiple type of oxidative stress and may be critical in preserving central vision.
Pascual
Iranzu
I
Mechanisms of Retinal Diseases Section, Laboratory of Retinal Cell and Molecular Biology, National eye institute, NIH, 6 Center Drive, MSC 0608 Bldg. 6 Bethesda, MD 20892, USA. pascuali@nei.nih.gov <pascuali@nei.nih.gov>
Larrayoz
Ignacio M
IM
Campos
Maria M
MM
Rodriguez
Ignacio R
IR
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D019610:Cytoprotection; D004791:Enzyme Inhibitors / Q000633:toxicity; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007653:Ketocholesterols / Q000633:toxicity; D007668:Kidney / Q000201:enzymology; D008253:Macaca mulatta; D051150:Methionine Sulfoxide Reductases; D008840:Microfilament Proteins; D018482:Muscle, Skeletal / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D012160:Retina / Q000201:enzymology*; D017949:Retinal Cone Photoreceptor Cells / Q000201:enzymology; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000201:enzymology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D014212:Tretinoin / Q000633:toxicity; D020122:tert-Butylhydroperoxide / Q000633:toxicity
D004791:Enzyme Inhibitors; D007653:Ketocholesterols; D008840:Microfilament Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D014212:Tretinoin; D020122:tert-Butylhydroperoxide; D010088:Oxidoreductases; C120376:MSRB2 protein, human; D051150:Methionine Sulfoxide Reductases; C003001:7-ketocholesterol