Evidence map›Paper›PMID 28951044›Full record

ArticleFree radical biology & medicine2017

Proteomic analysis of the glutathione-deficient LEGSKO mouse lens reveals activation of EMT signaling, loss of lens specific markers, and changes in stress response proteins.

Jeremy A Whitson, Phillip A Wilmarth, John Klimek, Vincent M Monnier, Larry David, Xingjun Fan

Abstract read
In one paragraph

Article in Free radical biology & medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

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  11. Advances in pharmacotherapy of cataracts.Annals of translational medicine · 2020
    Review
  12. Article
  13. Review
  14. Oxidative Stress Effects of Soluble Sulfide on Human Hepatocyte Cell Line LO2.International journal of environmental research and public health · 2019
    Article
  15. Article
  16. 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

6 authors at 3 institutions in 1 country.

Jeremy A WhitsonCase Western Reserve University, Department of Pathology, 2301 Cornell Rd, Cleveland, OH 44106, USA.
Phillip A WilmarthOregon Health Sciences University, Department of Biochemistry & Molecular Biology, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA.
John KlimekProteomics Shared Resource, Oregon Health & Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA.
Vincent M MonnierCase Western Reserve University, Department of Pathology, 2301 Cornell Rd, Cleveland, OH 44106, USA; Case Western Reserve University, Department of Biochemistry, 2109 Adelbert Road, Cleveland, OH 44106, USA.
Larry DavidOregon Health Sciences University, Department of Biochemistry & Molecular Biology, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA.
Xingjun FanCase Western Reserve University, Department of Pathology, 2301 Cornell Rd, Cleveland, OH 44106, USA. Electronic address: xxf3@case.edu.
Oregon Health & Science University · USCase Western Reserve University · USCornell University · US

Funding

Proteomics CoreP30EY010572 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Kate E Keller · 1995 to 2026
$19.4M
VISUAL SCIENCES TRAINING PROGRAMT32EY007157 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Johannes Friedrich von Lintig · 2000 to 2026
$5.5M
AMINO-CARBONYL REACTIONS IN THE AGING HUMAN LENSR01EY007099 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI MONNIER, VINCENT M · 1987 to 2016
$4.3M
Cole Eye Institute Vision Science Training ProgramT32EY024236 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI ANAND-APTE, BELA · 2015 to 2025
$1.0M
LTQ Orbitrap VelosS10OD012246 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI DAVID, LARRY L · 2012 to 2012
$854k
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 P30 EY010572NEI NIH HHS R01 EY007099NEI NIH HHS R21 EY024553NEI NIH HHS T32 EY007157NEI NIH HHS T32 EY024236NIH HHS S10 OD012246
6 · The paper itself

Abstract

purposeTo determine global protein expression changes in the lens of the GSH-deficient LEGSKO mouse model of age-related cataract for comparison with recently published gene expression data obtained by RNA-Seq transcriptome analysis.

methodsLenses were separated into epithelial and cortical fiber sections, digested with trypsin, and labeled with isobaric tags (10-plex TMT

results1871 proteins in lens epithelia and 870 proteins in lens fiber cells were quantified. 40 proteins in LEGSKO epithelia, 14 proteins in LEGSKO fiber cells, 22 proteins in buthionine sulfoximine (BSO)-treated LEGSKO epithelia, and 55 proteins in BSO-treated LEGSKO fiber cells had significantly (p<0.05, FDR<0.1) altered protein expression compared to WT controls. HSF4 and MAF transcription factors were the most common upstream regulators of the response to GSH-deficiency. Many detoxification proteins, including aldehyde dehydrogenases, peroxiredoxins, and quinone oxidoreductase, were upregulated but several glutathione S-transferases were downregulated. Several cellular stress response proteins showed regulation changes, including an upregulation of HERPUD1, downregulation of heme oxygenase, and mixed changes in heat shock proteins. NRF2-regulated proteins showed broad upregulation in BSO-treated LEGSKO fiber cells, but not in other groups. Strong trends were seen in downregulation of lens specific proteins, including β- and γ-crystallins, lengsin, and phakinin, and in epithelial-mesenchymal transition (EMT)-related changes. Western blot analysis of LEGSKO lens epithelia confirmed expression changes in several proteins.

conclusionsThis dataset confirms at the proteomic level many findings from the recently determined GSH-deficient lens transcriptome and provides new insight into the roles of GSH in the lens, how the lens adapts to oxidative stress, and how GSH affects EMT in the lens.

Indexed as

Epithelial-Mesenchymal TransitionSignal TransductionAnimalsCataractChromatography, LiquidGene Expression RegulationGlutathioneLens, CrystallineMaleMiceModels, AnimalOxidative StressProteomeProteomicsTandem Mass SpectrometryGlutathioneProteomeCataractEpithelial-mesenchymal transitionGlutathioneIsobaric taggingLEGSKO mouseNRF2Oxidative stressProteomicsTMT

Identifiers

PMID28951044
PMCPMC5699945
OpenAlexW2758432361

What OpenQuestion holds

Textmetadata
LicenceTDM
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.