Document Detail


Redox proteomic identification of visual arrestin dimerization in photoreceptor degeneration after photic injury.
MedLine Citation:
PMID:  22599583     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Light-induced oxidative stress is an important risk factor for age-related macular degeneration, but the downstream mediators of photoreceptor and retinal pigment epithelium cell death after photic injury are unknown. Given our previous identification of sulfhydryl/disulfide redox status as a factor in photoreceptor survival, we hypothesized that formation of one or more disulfide-linked homo- or hetero-dimeric proteins might signal photoreceptor death after light-induced injury.
METHODS: Two-dimensional (non-reducing/reducing) gel electrophoresis of Wistar rat retinal homogenates after 10 hours of 10,000 lux (4200°K) light in vivo, followed by mass spectrometry identification of differentially oxidized proteins.
RESULTS: The redox proteomic screen identified homodimers of visual arrestin (Arr1; S antigen) after toxic levels of light injury. Immunoblot analysis revealed a light duration-dependent formation of Arr1 homodimers, as well as other Arr1 oligomers. Immunoprecipitation studies revealed that the dimerization of Arr1 due to photic injury was distinct from association with its physiological binding partners, rhodopsin and enolase1. Systemic delivery of tris(2-carboxyethyl)phosphine, a specific disulfide reductant, both decreased Arr1 dimer formation and protected photoreceptors from light-induced degeneration in vivo.
CONCLUSIONS: These findings suggest a novel arrestin-associated pathway by which oxidative stress could result in cell death, and identify disulfide-dependent dimerization as a potential therapeutic target in retinal degeneration.
Authors:
Christopher J Lieven; Jonathan D Ribich; Megan E Crowe; Leonard A Levin
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-26
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  53     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-27     Completed Date:  2012-12-17     Revised Date:  2013-01-09    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3990-8     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arrestin / metabolism*
Arrestins / metabolism*
Dimerization*
Electrophoresis, Gel, Two-Dimensional
Immunoblotting
Immunoprecipitation
Light / adverse effects
Male
Mass Spectrometry
Optic Nerve Injuries / complications*,  metabolism,  pathology
Oxidation-Reduction
Oxidative Stress
Photoreceptor Cells / metabolism,  pathology*
Proteomics / methods*
Radiation Injuries, Experimental / complications,  metabolism,  pathology
Rats
Rats, Wistar
Retinal Degeneration / etiology,  metabolism*,  pathology
Grant Support
ID/Acronym/Agency:
P30 EY016665/EY/NEI NIH HHS; P30 EY016665/EY/NEI NIH HHS; R21 EY017970/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Arrestin; 0/Arrestins; 0/beta-arrestin

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