Evidence map›Paper›PMID 29775961›Full record

ReviewRedox biology2018

Antioxidant response elements: Discovery, classes, regulation and potential applications.

Azhwar Raghunath, Kiruthika Sundarraj, Raju Nagarajan, Frank Arfuso, Jinsong Bian, Alan P Kumar, Gautam Sethi, Ekambaram Perumal

Open access · goldAbstract readReview
In one paragraph

Review in Redox biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 258 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
258citing papers in PubMed, 2 pooled it
17.7field-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

258 citing papers in PubMed, 2 syntheses or guidelines pooled it, 459 citations in OpenAlex.

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198 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 4 institutions in 3 countries.

Azhwar RaghunathMolecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore 641046, Tamilnadu, India.
Kiruthika SundarrajMolecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore 641046, Tamilnadu, India.
Raju NagarajanDepartment of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, Tamilnadu, India.
Frank ArfusoStem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6009, Australia.
Jinsong BianDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600 Singapore, Singapore.
Alan P KumarDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600 Singapore, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; Medical Science Cluster, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, WA, Australia. Electronic address: csiapk@nus.edu.sg.
Gautam SethiDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600 Singapore, Singapore. Electronic address: phcgs@nus.edu.sg.
Ekambaram PerumalMolecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore 641046, Tamilnadu, India. Electronic address: ekas2009@buc.edu.in.
Bharathiar University · INNational University of Singapore · SGCurtin University · AUIndian Institute of Technology Madras · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Exposure to antioxidants and xenobiotics triggers the expression of a myriad of genes encoding antioxidant proteins, detoxifying enzymes, and xenobiotic transporters to offer protection against oxidative stress. This articulated universal mechanism is regulated through the cis-acting elements in an array of Nrf2 target genes called antioxidant response elements (AREs), which play a critical role in redox homeostasis. Though the Keap1/Nrf2/ARE system involves many players, AREs hold the key in transcriptional regulation of cytoprotective genes. ARE-mediated reporter constructs have been widely used, including xenobiotics profiling and Nrf2 activator screening. The complexity of AREs is brought by the presence of other regulatory elements within the AREs. The diversity in the ARE sequences not only bring regulatory selectivity of diverse transcription factors, but also confer functional complexity in the Keap1/Nrf2/ARE pathway. The different transcription factors either homodimerize or heterodimerize to bind the AREs. Depending on the nature of partners, they may activate or suppress the transcription. Attention is required for deeper mechanistic understanding of ARE-mediated gene regulation. The computational methods of identification and analysis of AREs are still in their infancy. Investigations are required to know whether epigenetics mechanism plays a role in the regulation of genes mediated through AREs. The polymorphisms in the AREs leading to oxidative stress related diseases are warranted. A thorough understanding of AREs will pave the way for the development of therapeutic agents against cancer, neurodegenerative, cardiovascular, metabolic and other diseases with oxidative stress.

Indexed as

Antioxidant Response ElementsAntioxidantsGene Expression RegulationHumansNeoplasmsNF-E2-Related Factor 2Oxidative StressSignal TransductionAntioxidantsNFE2L2 protein, humanNF-E2-Related Factor 2Antioxidant genesAntioxidant response elementsARE-reporter constructsARE SNPsKeap1/Nrf2/ARE pathwayOxidative stress

Identifiers

PMID29775961
PMCPMC6007815
OpenAlexW2800211923

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.