April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Post-Translational Modification of Differentially Expressed Mitochondrial Proteins in the Retina During Early EAU
Author Affiliations & Notes
  • T. Lee
    Pathology, Doheny Eye Institute, Los Angeles, California
  • S. Saraswathy
    Pathology, Doheny Eye Institute, Los Angeles, California
  • N. A. Rao
    Pathology, Doheny Eye Institute, Los Angeles, California
  • Footnotes
    Commercial Relationships  T. Lee, None; S. Saraswathy, None; N.A. Rao, None.
  • Footnotes
    Support  NIH grants: EY03040, EY019506, EY017347 and RPB
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5232. doi:
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      T. Lee, S. Saraswathy, N. A. Rao; Post-Translational Modification of Differentially Expressed Mitochondrial Proteins in the Retina During Early EAU. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5232.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Using proteomics, we demonstrated differential expression of mitochondrial proteins in the retina during early experimental autoimmune uveitis (EAU). Posttranslational protein modification plays an important role in cellular function and is a key event in signal transduction pathways leading to oxidative stress and DNA damage. We investigated posttranslational modification of differentially expressed proteins in retinal mitochondria during early EAU.

Methods: : EAU was induced in 12 B10RIII mice with 25 µg of interphotoreceptor retinoid-binding protein emulsified with complete Freund’s adjuvant (CFA); 12 mice treated with CFA alone served as controls. Retinas were dissected out from experimental and control groups on day 7 postimmunization; the mitochondrial fractions were extracted and subjected to 2D-DIGE. Protein spots indicating differential expression were subjected to MALDI-TOF for protein identification and indication of any post-translational modifications.

Results: : Of the 13 proteins differentially expressed by 2D-DIGE, 8 proteins (including upregulated aconitase, Hsp 70, βB2 crystallin, αA crystallin, syntaxin binding protein, and lamin, along with downregulated guanine nucleotide binding protein and ATP synthase) were found to undergo posttranslational modifications. Carbamidomethylation was found to occur on aconitase, Hsp 70, guanine nucleotide binding protein, ATP synthase, syntaxin binding protein, and lamin; Hsp70, ATP synthase, syntaxin and lamin were all oxidized in the EAU retina whereas βB2 crystallin experienced deamidation and αA crystallin had a pyro-glu modification.

Conclusions: : Retinal mitochondrial proteins are posttranslationally modified during early EAU indicating oxidative stress and mitochondrial DNA damage. The most common modifications are oxidation, carbamidomethylation and deamidation. A better understanding of proteins susceptible to posttranslational modification in the mitochondria at the early stage of the disease may help advance therapeutic intervention to attenuate disease progression.

Keywords: mitochondria • oxidation/oxidative or free radical damage • photoreceptors 
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