The oxidized thiol proteome in aging and cataractous mouse and human lens revealed by ICAT labeling

Benlian Wang, Grant Hom, Sheng Zhou, Minfei Guo, Binbin Li, Jing Yang, Vincent M. Monnier, Xingjun Fan

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Age-related cataractogenesis is associated with disulfide-linked high molecular weight (HMW) crystallin aggregates. We recently found that the lens crystallin disulfidome was evolutionarily conserved in human and glutathione-depleted mouse (LEGSKO) cataracts and that it could be mimicked by oxidation in vitro (Mol. Cell Proteomics, 14, 3211-23 (2015)). To obtain a comprehensive blueprint of the oxidized key regulatory and cytoskeletal proteins underlying cataractogenesis, we have now used the same approach to determine, in the same specimens, all the disulfide-forming noncrystallin proteins identified by ICAT proteomics. Seventy-four, 50, and 54 disulfide-forming proteins were identified in the human and mouse cataracts and the in vitro oxidation model, respectively, of which 17 were common to all three groups. Enzymes with oxidized cysteine at critical sites include GAPDH (hGAPDH, Cys247), glutathione synthase (hGSS, Cys294), aldehyde dehydrogenase (hALDH1A1, Cys126 and Cys186), sorbitol dehydrogenase (hSORD, Cys140, Cys165, and Cys179), and PARK7 (hPARK7, Cys46 and Cys53). Extensive oxidation was also present in lens-specific intermediate filament proteins, such as BFSP1 and BFSP12 (hBFSP1 and hBFSP12, Cys167, Cys65, and Cys326), vimentin (mVim, Cys328), and cytokeratins, as well as microfilament and microtubule filament proteins, such as tubulin and actins. While the biological impact of these modifications for lens physiology remains to be determined, many of these oxidation sites have already been associated with either impaired metabolism or cytoskeletal architecture, strongly suggesting that they have a pathogenic role in cataractogenesis. By extrapolation, these findings may be of broader significance for age- and disease-related dysfunctions associated with oxidant stress.

Original languageEnglish (US)
Pages (from-to)244-261
Number of pages18
JournalAging Cell
Volume16
Issue number2
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Fingerprint

Proteome
Sulfhydryl Compounds
Disulfides
Lenses
Crystallins
Proteomics
Cataract
Glutathione Synthase
L-Iditol 2-Dehydrogenase
Microtubule Proteins
Aldehyde Dehydrogenase
Cytoskeletal Proteins
Vimentin
Tubulin
Keratins
Actin Cytoskeleton
Oxidants
Glutathione
Cysteine
Actins

Keywords

  • aging
  • cataractogenesis
  • disulfide
  • mass spectrometry
  • proteomics
  • reactive oxygen species

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

The oxidized thiol proteome in aging and cataractous mouse and human lens revealed by ICAT labeling. / Wang, Benlian; Hom, Grant; Zhou, Sheng; Guo, Minfei; Li, Binbin; Yang, Jing; Monnier, Vincent M.; Fan, Xingjun.

In: Aging Cell, Vol. 16, No. 2, 01.04.2017, p. 244-261.

Research output: Contribution to journalArticle

Wang, B, Hom, G, Zhou, S, Guo, M, Li, B, Yang, J, Monnier, VM & Fan, X 2017, 'The oxidized thiol proteome in aging and cataractous mouse and human lens revealed by ICAT labeling', Aging Cell, vol. 16, no. 2, pp. 244-261. https://doi.org/10.1111/acel.12548
Wang, Benlian ; Hom, Grant ; Zhou, Sheng ; Guo, Minfei ; Li, Binbin ; Yang, Jing ; Monnier, Vincent M. ; Fan, Xingjun. / The oxidized thiol proteome in aging and cataractous mouse and human lens revealed by ICAT labeling. In: Aging Cell. 2017 ; Vol. 16, No. 2. pp. 244-261.
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