DJ-1-dependent regulation of oxidative stress in the retinal pigment epithelium (RPE)

DJ-1 is found in many tissues, including the brain, where it has been extensively studied due to its association with Parkinson's disease. DJ-1 functions as a redox-sensitive molecular chaperone and transcription regulator that robustly protects cells from oxidative stress. Retinal pigment epit...

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Bibliographic Details
Published in:PloS one 2013-07, Vol.8 (7), p.e67983
Main Authors: Shadrach, Karen G, Rayborn, Mary E, Hollyfield, Joe G, Bonilha, Vera L
Format: Article
Language:English
Subjects:
Adenoviruses
Age
Amino acids
Animals
Apolipoproteins
Apoptosis
Atrophy
Biology
Biomarkers
Blotting, Western
Brain
Brain research
Cancer
Cell culture
Cell Line
Cell Nucleus - metabolism
Cells, Cultured
Chemistry
Cytoplasm - metabolism
Epithelium
Eye
Eye (anatomy)
HEK293 Cells
Humans
Hydrogen peroxide
Hydrogen Peroxide - pharmacology
Immunohistochemistry
Immunoreactivity
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Kinases
Localization
Lysates
Macular degeneration
Macular Degeneration - metabolism
Macular Degeneration - pathology
Medicine
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Mitochondria
Mitochondria - metabolism
Mutation
Oncogene Proteins - genetics
Oncogene Proteins - metabolism
Oxidants - pharmacology
Oxidation-Reduction
Oxidative Stress
Oxygen
PARK7 protein
Photoreceptors
Physiology
Protein Deglycase DJ-1
Protein Transport - drug effects
Proteins
Reactive oxygen species
Reactive Oxygen Species - metabolism
Retina
Retinal pigment epithelium
Retinal Pigment Epithelium - cytology
Retinal Pigment Epithelium - drug effects
Retinal Pigment Epithelium - metabolism
Rodents
Serine
Tissues
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Summary:DJ-1 is found in many tissues, including the brain, where it has been extensively studied due to its association with Parkinson's disease. DJ-1 functions as a redox-sensitive molecular chaperone and transcription regulator that robustly protects cells from oxidative stress. Retinal pigment epithelial (RPE) cultures were treated with H2O2 for various times followed by biochemical and immunohistological analysis. Cells were transfected with adenoviruses carrying the full-length human DJ-1 cDNA and a mutant construct, which has the cysteine residues at amino acid 46, 53 and 106 mutated to serine (C to S) prior to stress experiments. DJ-1 localization, levels of expression and reactive oxygen species (ROS) generation were also analyzed in cells expressing exogenous DJ-1 under baseline and oxidative stress conditions. The presence of DJ-1 and oxidized DJ-1 was evaluated in human RPE total lysates. The distribution of DJ-1 was assessed in AMD and non-AMD cryosectionss and in isolated human Bruch's membrane (BM)/choroid from AMD eyes. DJ-1 in RPE cells under baseline conditions, displays a diffuse cytoplasmic and nuclear staining. After oxidative challenge, more DJ-1 was associated with mitochondria. Increasing concentrations of H2O2 resulted in a dose-dependent increase in DJ-1. Overexpression of DJ-1 but not the C to S mutant prior to exposure to oxidative stress led to significant decrease in the generation of ROS. DJ-1 and oxDJ-1 intensity of immunoreactivity was significantly higher in the RPE lysates from AMD eyes. More DJ-1 was localized to RPE cells from AMD donors with geographic atrophy and DJ-1 was also present in isolated human BM/choroid from AMD eyes. DJ-1 regulates RPE responses to oxidative stress. Most importantly, increased DJ-1 expression prior to oxidative stress leads to decreased generation of ROS, which will be relevant for future studies of AMD since oxidative stress is a known factor affecting this disease.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0067983