Evidence map›Paper›PMID 20805060›Full record

ArticleEnvironmental health perspectives2011

Long isoforms of NRF1 contribute to arsenic-induced antioxidant response in human keratinocytes.

Rui Zhao, Yongyong Hou, Peng Xue, Courtney G Woods, Jingqi Fu, Bo Feng, Dawei Guan, Guifan Sun, Jefferson Y Chan, Michael P Waalkes and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Environmental health perspectives, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.

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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

12 authors at 4 institutions in 2 countries.

Rui ZhaoSchool of Forensic Medicine, China Medical University, Shenyang, China.
Yongyong Hou
Peng Xue
Courtney G Woods
Jingqi Fu
Bo Feng
Dawei Guan
Guifan Sun
Jefferson Y Chan
Michael P Waalkes
Melvin E Andersen
Jingbo Pi
The Hamner Institutes for Health Sciences · USChina Medical University · CNNational Institutes of Health · USUniversity of California, Irvine · US

Funding

Stem Cell ToxicologyZIAES102925 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI TOKAR, ERIK · 2010 to 2021
$25.3M
Paradoxical roles of Nrf2 activation in arsenic-induced beta-cell dysfunctionR01ES016005 · NIEHS · THE HAMNER INSTITUTES · PI PI, JINGBO · 2008 to 2012
$2.5M
Intramural NIH HHSNIEHS NIH HHS ES016005NIEHS NIH HHS R01 ES016005
6 · The paper itself

Abstract

backgroundHuman exposure to inorganic arsenic (iAs), a potent oxidative stressor, causes various dermal disorders, including hyperkeratosis and skin cancer. Nuclear factor-erythroid 2-related factor 1 (NRF1, also called NFE2L1) plays a critical role in regulating the expression of many antioxidant response element (ARE)-dependent genes.

objectivesWe investigated the role of NRF1 in arsenic-induced antioxidant response and cytotoxicity in human keratinocytes.

resultsIn cultured human keratinocyte HaCaT cells, inorganic arsenite (iAs3+) enhanced the protein accumulation of long isoforms (120-140 kDa) of NRF1 in a dose- and time-dependent fashion. These isoforms accumulated mainly in the nuclei of HaCaT cells. Selective deficiency of NRF1 by lentiviral short-hairpin RNAs in HaCaT cells [NRF1-knockdown (KD)] led to decreased expression of γ-glutamate cysteine ligase catalytic subunit (GCLC) and regulatory subunit (GCLM) and a reduced level of intracellular glutathione. In response to acute iAs3+ exposure, induction of some ARE-dependent genes, including NAD(P)H:quinone oxidoreductase 1 (NQO1), GCLC, and GCLM, was significantly attenuated in NRF1-KD cells. However, the iAs3-induced expression of heme oxygenase 1 (HMOX-1) was unaltered by silencing NRF1, suggesting that HMOX-1 is not regulated by NRF1. In addition, the lack of NRF1 in HaCaT cells did not disturb iAs3+-induced NRF2 accumulation but noticeably decreased Kelch-like ECH-associated protein 1 (KEAP1) levels under basal and iAs3+-exposed conditions, suggesting a potential interaction between NRF1 and KEAP1. Consistent with the critical role of NRF1 in the transcriptional regulation of some ARE-bearing genes, knockdown of NRF1 significantly increased iAs3+-induced cytotoxicity and apoptosis.

conclusionsHere, we demonstrate for the first time that long isoforms of NRF1 contribute to arsenic-induced antioxidant response in human keratinocytes and protect the cells from acute arsenic cytotoxicity.

Indexed as

AntioxidantsArsenicCell LineDose-Response Relationship, DrugEnvironmental PollutantsHumansKeratinocytesNF-E2-Related Factor 1Oxidative StressProtein IsoformsRNA, MessengerAntioxidantsArsenicEnvironmental PollutantsNF-E2-Related Factor 1Protein IsoformsRNA, Messenger

Identifiers

PMID20805060
PMCPMC3018500
OpenAlexW2017722997

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Registered trials

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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.