Evidence map›Paper›PMID 21832082›Full record

ArticleThe Journal of biological chemistry2011

Thioredoxin reductase-2 is essential for keeping low levels of H(2)O(2) emission from isolated heart mitochondria.

Brian A Stanley, Vidhya Sivakumaran, Sa Shi, Iain McDonald, David Lloyd, Walter H Watson, Miguel A Aon, Nazareno Paolocci

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

112 citing papers in PubMed, 193 citations in OpenAlex.

  1. Article
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  12. Effects of ROS pathway inhibitors and NADH and FADHArchives of biochemistry and biophysics · 2023
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Computational modeling of mitochondrial KJournal of molecular and cellular cardiology · 2022
    Article
  19. Observational
  20. Review

52 more citing papers are in PubMed but not listed here.

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

8 authors at 5 institutions in 4 countries.

Brian A StanleyDivision of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Vidhya Sivakumaran
Sa Shi
Iain McDonald
David Lloyd
Walter H Watson
Miguel A Aon
Nazareno Paolocci
Cardiff University · GBJohns Hopkins University · USHarbin Medical University · CNJohns Hopkins Medicine · USUniversity of Louisville · US

Funding

Mechanisms Underlying Mitrochondrial Dysfunction in the Diabetic HeartR01HL091923 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI AKAR, FADI GABRIEL, AON, MIGUEL ANTONIO · 2009 to 2012
$1.9M
NHLBI NIH HHS R01 HL091923NHLBI NIH HHS R01-HL091923-01
6 · The paper itself

Abstract

Respiring mitochondria produce H(2)O(2) continuously. When production exceeds scavenging, H(2)O(2) emission occurs, endangering cell functions. The mitochondrial peroxidase peroxiredoxin-3 reduces H(2)O(2) to water using reducing equivalents from NADPH supplied by thioredoxin-2 (Trx2) and, ultimately, thioredoxin reductase-2 (TrxR2). Here, the contribution of this mitochondrial thioredoxin system to the control of H(2)O(2) emission was studied in isolated mitochondria and cardiomyocytes from mouse or guinea pig heart. Energization of mitochondria by the addition of glutamate/malate resulted in a 10-fold decrease in the ratio of oxidized to reduced Trx2. This shift in redox state was accompanied by an increase in NAD(P)H and was dependent on TrxR2 activity. Inhibition of TrxR2 in isolated mitochondria by auranofin resulted in increased H(2)O(2) emission, an effect that was seen under both forward and reverse electron transport. This effect was independent of changes in NAD(P)H or membrane potential. The effects of auranofin were reproduced in cardiomyocytes; superoxide and H(2)O(2) levels increased, but similarly, there was no effect on NAD(P)H or membrane potential. These data show that energization of mitochondria increases the antioxidant potential of the TrxR2/Trx2 system and that inhibition of TrxR2 results in increased H(2)O(2) emission through a mechanism that is independent of changes in other redox couples.

Indexed as

AnimalsAuranofinDinitrochlorobenzeneElectron TransportEnergy MetabolismEnzyme AssaysGlutathioneGuinea PigsHydrogen PeroxideMiceMitochondria, HeartMyocytes, CardiacOxidation-ReductionPeroxiredoxin IIIThioredoxin Reductase 2ThioredoxinsAuranofinDinitrochlorobenzeneGlutathioneHydrogen PeroxidePeroxiredoxin IIIThioredoxin Reductase 2Thioredoxins

Identifiers

PMID21832082
PMCPMC3190932
OpenAlexW2000954596

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.