Evidence map›Paper›PMID 24191235›Full record

ArticleRedox biology2013

Nrf2 activation supports cell survival during hypoxia and hypoxia/reoxygenation in cardiomyoblasts; the roles of reactive oxygen and nitrogen species.

Rajitha T Kolamunne, Irundika H K Dias, Ann B Vernallis, Melissa M Grant, Helen R Griffiths

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.6field-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

42 citing papers in PubMed, 74 citations in OpenAlex.

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  17. Understanding the role of the cytoprotective transcription factor nuclear factor erythroid 2-related factor 2-lessons from evolution, the animal kingdom and rare progeroid syndromes.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2020
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  19. Protective effect of the extremolytes ectoine and hydroxyectoine in a porcine organ culture.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2020
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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

5 authors at 2 institutions in 1 country.

Rajitha T KolamunneLife and Health Sciences, Aston University, Birmingham, B4 7ET, UK ; Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Irundika H K Dias
Ann B Vernallis
Melissa M Grant
Helen R Griffiths
Aston University · GBUniversity of Birmingham · GB

Funding

The Dunhill Medical Trust R92/1108
6 · The paper itself

Abstract

Adaptive mechanisms involving upregulation of cytoprotective genes under the control of transcription factors such as Nrf2 exist to protect cells from permanent damage and dysfunction under stress conditions. Here we explore of the hypothesis that Nrf2 activation by reactive oxygen and nitrogen species modulates cytotoxicity during hypoxia (H) with and without reoxygenation (H/R) in H9C2 cardiomyoblasts. Using MnTBap as a cell permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger and L-NAME as an inhibitor of nitric oxide synthase (NOS), we have shown that MnTBap inhibited the cytotoxic effects of hypoxic stress with and without reoxygenation. However, L-NAME only afforded protection during H. Under reoxygenation, conditions, cytotoxicity was increased by the presence of L-NAME. Nrf2 activation was inhibited independently by MnTBap and L-NAME under H and H/R. The increased cytotoxicity and inhibition of Nrf2 activation by the presence of L-NAME during reoxygenation suggests that NOS activity plays an important role in cell survival at least in part via Nrf2-independent pathways. In contrast, O2 (-•) scavenging by MnTBap prevented both toxicity and Nrf2 activation during H and H/R implying that toxicity is largely dependent on O2 (-•).To confirm the importance of Nrf2 for myoblast metabolism, Nrf2 knockdown with siRNA reduced cell survival by 50% during 4 h hypoxia with and without 2 h of reoxygenation and although cellular glutathione (GSH) was depleted during H and H/R, GSH loss was not exacerbated by Nrf2 knockdown. These data support distinctive roles for ROS and RNS during H and H/R for Nrf2 induction which are important for survival independently of GSH salvage.

Indexed as

AnimalsCell HypoxiaCells, CulturedCell SurvivalGene Knockdown TechniquesMetalloporphyrinsMyoblasts, CardiacNF-E2-Related Factor 2NG-Nitroarginine Methyl EsterRatsReactive Nitrogen SpeciesReactive Oxygen Speciesmanganese(III)-tetrakis(4-benzoic acid)porphyrinMetalloporphyrinsNfe2l2 protein, ratNF-E2-Related Factor 2NG-Nitroarginine Methyl EsterReactive Nitrogen SpeciesReactive Oxygen SpeciesAdaptiveCREB, cAMP-responsive element-binding proteinDAF-2-DA, 4,5-diaminofluorescein diacetateDHE, dihydroethidiumGlutathioneHIF-1, hypoxia-inducible factorKEAP1, Kelch-like ECH-associated protein 1L-NAMEL-NAME, L-NG-nitroarginine methyl esterMnTBapMnTBap, manganese [III] tetrakis (4-benzoic acid) porphyrinNFκB, nuclear factor kappa BNO, nitric oxideNOS, nitric oxide synthaseNOX, NADPH oxidaseNrf2, nuclear factor erythroid 2-related factor 2RNSRNS, reactive nitrogen speciesROSROS, reactive oxygen species

Identifiers

PMID24191235
PMCPMC3814985
OpenAlexW1983709983

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.