Evidence map›Paper›PMID 26058897›Full record

ReviewAntioxidants & redox signaling2015

TrxR1 as a potent regulator of the Nrf2-Keap1 response system.

Marcus Cebula, Edward E Schmidt, Elias S J Arnér

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed, 1 pooled it
9.9field-weighted citation impact, top 1% 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

135 citing papers in PubMed, 1 synthesis or guideline pooled it, 244 citations in OpenAlex.

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75 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

3 authors at 2 institutions in 2 countries.

Marcus Cebula1 Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet , Stockholm, Sweden .
Edward E Schmidt2 Microbiology and Immunology, Montana State University , Bozeman, Montana.
Elias S J Arnér1 Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet , Stockholm, Sweden .
Karolinska Institutet · SEMontana State University · US

Funding

Impact of hepatocyte lineage life history dynamics on liver homeostasis in the agR01AG040020 · NIA · MONTANA STATE UNIVERSITY - BOZEMAN · PI GEDEON, TOMAS, SCHMIDT, EDWARD E · 2011 to 2015
$1.5M
NIA NIH HHS R01 AG040020
6 · The paper itself

Abstract

significanceAll cells must maintain a balance between oxidants and reductants, while allowing for fluctuations in redox states triggered by signaling, altered metabolic flow, or extracellular stimuli. Furthermore, they must be able to rapidly sense and react to various challenges that would disrupt the redox homeostasis. RECENT ADVANCES: Many studies have identified Keap1 as a key sensor for oxidative or electrophilic stress, with modification of Keap1 by oxidation or electrophiles triggering Nrf2-mediated transcriptional induction of enzymes supporting reductive and detoxification pathways. However, additional mechanisms for Nrf2 regulation are likely to exist upstream of, or in parallel with, Keap1. CRITICAL ISSUES: Here, we propose that the mammalian selenoprotein thioredoxin reductase 1 (TrxR1) is a potent regulator of Nrf2. A high chemical reactivity of TrxR1 and its vital role for the thioredoxin (Trx) system distinguishes TrxR1 as a prime target for electrophilic challenges. Chemical modification of the selenocysteine (Sec) in TrxR1 by electrophiles leads to rapid inhibition of thioredoxin disulfide reductase activity, often combined with induction of NADPH oxidase activity of the derivatized enzyme, thereby affecting many downstream redox pathways. The notion of TrxR1 as a regulator of Nrf2 is supported by many publications on effects in human cells of selenium deficiency, oxidative stress or electrophile exposure, as well as the phenotypes of genetic mouse models. FUTURE DIRECTIONS: Investigation of the role of TrxR1 as a regulator of Nrf2 activation will facilitate further studies of redox control in diverse cells and tissues of mammals, and possibly also in animals of other classes.

Indexed as

Signal TransductionAnimalsHumansIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2Oxidation-ReductionSelenocysteineThioredoxin Reductase 1Intracellular Signaling Peptides and ProteinsKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2SelenocysteineThioredoxin Reductase 1

Identifiers

PMID26058897
PMCPMC4589110
OpenAlexW1802175835

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.