Evidence map›Paper›PMID 26438826›Full record

ArticleThe Journal of biological chemistry2015

High Glucose-induced Retinal Pericyte Apoptosis Depends on Association of GAPDH and Siah1.

Sandra Suarez, Gary W McCollum, Ashwath Jayagopal, John S Penn

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

20 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Article
  3. New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025
    Review
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  13. Article
  14. Article
  15. Article
  16. Pericytes: Problems and Promises for CNS Repair.Frontiers in cellular neuroscience · 2019
    Article
  17. Article
  18. Integrative medicine research · 2017
    Article
  19. Article
  20. CAF cellular glycolysis: linking cancer cells with the microenvironment.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Review
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

4 authors at 2 institutions in 2 countries.

Sandra SuarezDepartments of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8808. Electronic address: Sandra.suarez@vanderbilt.edu.
Gary W McCollumDepartments of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8808.
Ashwath JayagopalPharma Research and Early Development (pRED), F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
John S PennDepartments of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8808; Departments of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8808.
Vanderbilt University · USRoche (Switzerland) · CH

Funding

The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David J. Calkins · 1989 to 2026
$19.6M
Vanderbilt/Meharry Initiative for Minority Student DvptR25GM062459 · NIGMS · VANDERBILT UNIVERSITY · PI VELEZ EDWARDS, DIGNA R · 2002 to 2020
$10.4M
RETINOPATHY OF PREMATURITY--UNDERSTAND ITS PATHOGENESISR01EY007533 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PENN, JOHN S. · 1993 to 2018
$7.0M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)KL2TR000446 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$2.8M
The calcineurin/NFAT signaling axis in diabetic retinopathy pathogenesisR01EY023639 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PENN, JOHN S. · 2014 to 2017
$1.8M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)TL1TR000447 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$1.2M
LSM880-Airyscan Confocal Microscope for Large Shared ResourceS10OD021630 · OD · VANDERBILT UNIVERSITY · PI WELLS, K. SAM · 2016 to 2016
$560k
NCATS NIH HHS KL2 TR000446NCATS NIH HHS KL2TR000446NCATS NIH HHS TL1 TR000447NCATS NIH HHS TL1TR000447NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1TR000445NEI NIH HHS P30 EY008126NEI NIH HHS R01 EY007533NEI NIH HHS R01 EY023639NEI NIH HHS R01 EY07533NEI NIH HHS R01 EY07533-S25-27NIGMS NIH HHS R25 GM062459NIH HHS S10 OD021630
6 · The paper itself

Abstract

Diabetic retinopathy (DR) is a leading cause of blindness worldwide, and its prevalence is growing. Current therapies for DR address only the later stages of the disease, are invasive, and have limited effectiveness. Retinal pericyte death is an early pathologic feature of DR. Although it has been observed in diabetic patients and in animal models of DR, the cause of pericyte death remains unknown. A novel pro-apoptotic pathway initiated by the interaction between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the E3 ubiquitin ligase, seven in absentia homolog 1 (Siah1), was recently identified in ocular tissues. In this article we examined the involvement of the GAPDH/Siah1 interaction in human retinal pericyte (hRP) apoptosis. HRP were cultured in 5 mm normal glucose, 25 mm l- or d-glucose for 48 h (osmotic control and high glucose treatments, respectively). Siah1 siRNA was used to down-regulate Siah1 expression. TAT-FLAG GAPDH and/or Siah1-directed peptides were used to block GAPDH and Siah1 interaction. Co-immunoprecipitation assays were conducted to analyze the effect of high glucose on the association of GAPDH and Siah1. Apoptosis was measured by Annexin V staining and caspase-3 enzymatic activity assay. High glucose increased Siah1 total protein levels, induced the association between GAPDH and Siah1, and led to GAPDH nuclear translocation. Our findings demonstrate that dissociation of the GAPDH/Siah1 pro-apoptotic complex can block high glucose-induced pericyte apoptosis, widely considered a hallmark feature of DR. Thus, the work presented in this article can provide a foundation to identify novel targets for early treatment of DR.

Indexed as

ApoptosisCell NucleusCells, CulturedGene Knockdown TechniquesGlucoseGlyceraldehyde-3-Phosphate DehydrogenasesHumansNuclear ProteinsPericytesProtein TransportRetinaSeven in Absentia ProteinsUbiquitin-Protein LigasesGlucoseGlyceraldehyde-3-Phosphate DehydrogenasesNuclear ProteinsSeven in Absentia ProteinsUbiquitin-Protein Ligasesapoptosiscell signalingdiabetesdiabetic retinopathyGAPDHglucoseretinaSiah1

Identifiers

PMID26438826
PMCPMC4653686
OpenAlexW2285733306

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.