Evidence map›Paper›PMID 26453637›Full record

ArticleMolecular & cellular proteomics : MCP2015

Evidence of Highly Conserved β-Crystallin Disulfidome that Can be Mimicked by In Vitro Oxidation in Age-related Human Cataract and Glutathione Depleted Mouse Lens.

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

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 53 citations in OpenAlex.

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  14. Review
  15. Aging lens epithelium is susceptible to ferroptosis.Free radical biology & medicine · 2021
    Article
  16. Broadening the Mutation Spectrum inFrontiers in medicine · 2021
    Article
  17. Review
  18. Molecular Processes Implicated in Human Age-Related Nuclear Cataract.Investigative ophthalmology & visual science · 2019
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Xingjun FanFrom the ‡Department of Pathology, xxf3@case.edu vmm3@case.edu.ORCID http://orcid.org/0000-0002-6477-4465
Sheng Zhou¶State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China;
Benlian Wang‖Center for Proteomics.
Grant Hom**Fairview High School, Fairview, Ohio;
Minfei Guo‡‡Department of Ophthalmology, the Huichang County People's Hospital, Jiangxi, China;
Binbin Li§§Department of Ophthalmology, Ganzhou City People's Hospital, Jiangxi, China.
Jing Yang¶State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China;
Dennis VaysburgFrom the ‡Department of Pathology.
Vincent M MonnierFrom the ‡Department of Pathology, §Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44120; xxf3@case.edu vmm3@case.edu.
Sun Yat-sen University · CNCase Western Reserve University · USFairview School District · USGanzhou People's Hospital · CNHuizhou Central People's Hospital · CN

Funding

TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
AMINO-CARBONYL REACTIONS IN THE AGING HUMAN LENSR01EY007099 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI MONNIER, VINCENT M · 1987 to 2016
$4.3M
Molecular characterization of the glutathione transport system in the lensR21EY024553 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI FAN, XINGJUN · 2015 to 2016
$436k
NEI NIH HHS EY024553NEI NIH HHS EY07099NEI NIH HHS P30 EY011373NEI NIH HHS R01 EY007099NEI NIH HHS R21 EY024553
6 · The paper itself

Abstract

Low glutathione levels are associated with crystallin oxidation in age-related nuclear cataract. To understand the role of cysteine residue oxidation, we used the novel approach of comparing human cataracts with glutathione-depleted LEGSKO mouse lenses for intra- versus intermolecular disulfide crosslinks using 2D-PAGE and proteomics, and then systematically identified in vivo and in vitro all disulfide forming sites using ICAT labeling method coupled with proteomics. Crystallins rich in intramolecular disulfides were abundant at young age in human and WT mouse lens but shifted to multimeric intermolecular disulfides at older age. The shift was ∼4x accelerated in LEGSKO lens. Most cysteine disulfides in β-crystallins (except βA4 in human) were highly conserved in mouse and human and could be generated by oxidation with H(2)O(2), whereas γ-crystallin oxidation selectively affected γC23/42/79/80/154, γD42/33, and γS83/115/130 in human cataracts, and γB79/80/110, γD19/109, γF19/79, γE19, γS83/130, and γN26/128 in mouse. Analysis based on available crystal structure suggests that conformational changes are needed to expose Cys42, Cys79/80, Cys154 in γC; Cys42, Cys33 in γD, and Cys83, Cys115, and Cys130 in γS. In conclusion, the β-crystallin disulfidome is highly conserved in age-related nuclear cataract and LEGSKO mouse, and reproducible by in vitro oxidation, whereas some of the disulfide formation sites in γ-crystallins necessitate prior conformational changes. Overall, the LEGSKO mouse model is closely reminiscent of age-related nuclear cataract.

Indexed as

AgingAnimalsbeta-CrystallinsCataractCell LineCysteineDisease Models, AnimalDisulfidesGlutathioneHumansIn Vitro TechniquesLens, CrystallineMiceOxidation-ReductionProtein ConformationProteomicsbeta-CrystallinsCysteineDisulfidesGlutathione

Identifiers

PMID26453637
PMCPMC4762625
OpenAlexW2178481958

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.