Evidence map›Paper›PMID 21194376›Full record

ArticleAntioxidants & redox signaling2011

Hsp90 regulates NADPH oxidase activity and is necessary for superoxide but not hydrogen peroxide production.

Feng Chen, Deepesh Pandey, Ahmed Chadli, John D Catravas, Teng Chen, David J R Fulton

Abstract read
In one paragraph

Article in Antioxidants & redox signaling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

50 citing papers in PubMed, 81 citations in OpenAlex.

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  10. Article
  11. Oxidative Stress and the Role of NADPH Oxidase in Glaucoma.Antioxidants (Basel, Switzerland) · 2021
    Review
  12. NOX Inhibitors: From Bench to Naxibs to Bedside.Handbook of experimental pharmacology · 2021
    Article
  13. Article
  14. Article
  15. Article
  16. Article
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  20. 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

6 authors at 3 institutions in 3 countries.

Feng ChenDepartment of Forensic Sciences, Xi'an Jiaotong University School of Medicine, Xi'an Shaanxi, P.R. China.
Deepesh Pandey
Ahmed Chadli
John D Catravas
Teng Chen
David J R Fulton
Augusta University · USNational Cancer Center of Georgia · GEXi'an Jiaotong University · CN

Funding

Metabolic Determinants of Cardiovascular Dysfunction in ObesityR01HL092446 · NHLBI · AUGUSTA UNIVERSITY · PI FULTON, DAVID J, STEPP, DAVID W · 2009 to 2013
$2.1M
Tyrosine phosphorylation of endothelial nitric oxide synthaseR01HL085827 · NHLBI · AUGUSTA UNIVERSITY · PI FULTON, DAVID J · 2007 to 2011
$1.8M
VASCULAR ANTI-INFLAMMATORY ACTIONS OF HSP90 INHIBITORSR01HL093460 · NHLBI · OLD DOMINION UNIVERSITY · PI CATRAVAS, JOHN D · 2010 to 2013
$1.4M
NHLBI NIH HHS HL085827NHLBI NIH HHS HL092446NHLBI NIH HHS R01 HL085827NHLBI NIH HHS R01 HL093460
6 · The paper itself

Abstract

The goal of this study was to identify whether heat-shock protein 90 (Hsp90) regulates the production of superoxide and other reactive oxygen species from the NADPH oxidases (Nox). We found that pharmacological and genetic inhibition of Hsp90 directly reduced Nox5-derived superoxide without secondarily modifying signaling events. Coimmunoprecipitation and bioluminescence resonance energy transfer studies suggest that the C-terminus of Nox5 binds to Hsp90. Long-term Hsp90 inhibition reduced Nox5 expression and provides further evidence that Nox5 is an Hsp90 client protein. Inhibitors of Hsp90 also reduced superoxide from Nox1, Nox2 (neutrophils), and Nox3. However, Nox4, which emits only hydrogen peroxide, was unaffected by Hsp90 inhibitors. Hydrogen peroxide production from the other Nox enzymes was not affected by short-term inhibition of Hsp90, but long-term inhibition reduced production of all reactive oxygen species coincident with loss of enzyme expression. Expression of chimeric Nox enzymes consisting of N-terminal Nox1 or Nox3 and C-terminal Nox4 resulted in only hydrogen peroxide formation that was insensitive to Hsp90 inhibitors. We conclude that Hsp90 binds to the C-terminus of Noxes1-3 and 5 and is necessary for enzyme stability and superoxide production. Hsp90 does not bind to the C-terminus of Nox4 and is not required for hydrogen peroxide formation.

Indexed as

AnimalsBenzoquinonesChlorocebus aethiopsCOS CellsEnzyme AssaysHEK293 CellsHSP90 Heat-Shock ProteinsHumansHydrogen PeroxideImmunoprecipitationLactams, MacrocyclicMembrane ProteinsNADPH Oxidase 5NADPH OxidasesPhosphorylationProtein BindingBenzoquinonesHSP90 Heat-Shock ProteinsHydrogen PeroxideLactams, MacrocyclicMembrane ProteinsNADPH Oxidase 5NADPH OxidasesNOX5 protein, humanRecombinant ProteinsSuperoxidestanespimycin

Identifiers

PMID21194376
PMCPMC3085945
OpenAlexW2049373116

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.