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Cited by 113Genomics, phytochemicals, and oxidative stressRedox biology and oxidative stressGlutathione Transferases and Polymorphisms

Identification of aldo-keto reductases as NRF2-target marker genes in human cells

Jung, Kyeong-Ah, Choi, Bo-hyun, Nam, Chang-Won, Song, Mingu, Kim, Sang-Tae, Lee, Joo Young, Kwak, Mi-Kyoung·2013·Toxicology Letters
DOI 10.1016/j.toxlet.2012.12.026
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Abstract

Transcription factor NF-E2-related factor 2 (NRF2) plays a crucial role in the cellular defense against oxidative/electrophilic stress by up-regulating multiple antioxidant genes. Numerous studies with genetically modified animals have demonstrated that Nrf2 is a sensitivity determining factor upon the exposure to environmental chemicals including carcinogens. Moreover, recent studies have demonstrated that polymorphism in the human NRF2 promoter is associated with higher risks for developing acute lung injury, gastric mucosal inflammation, and nephritis. Therefore, the identification of reliable and effective human target genes of NRF2 may allow the monitoring of NRF2 activity and to predict individual sensitivity to environmental stress-induced damage. For this purpose, we investigated genes that are tightly controlled by NRF2 to establish markers for NRF2 activity in human cells. Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments. Accordantly, the basal and inducible expressions of AKRs were significantly attenuated in NRF2-silenced HK-2 cells. Whereas, cells with stable KEAP1 knockdown, which causes a modest NRF2 activation, demonstrated substantially increased levels of AKR1A1, 1B1, 1B10, 1C1, 1C2…

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  • All ApoE isoforms increased the expression of known NRF2 target genes including SLC7A11, AKR1C1, and FTH1.

    “and increased the expression of known target genes of this transcription factor including SLC7A11, AKR1C1, and FTH1 (fig. S5S) (41–45).”

    From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [41]

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References 58 · Cited by 113

Authors
Jung, K.-A., Choi, B.-H., Nam, C.-W., Song, M., Kim, S.-T., Lee, J. Y., & Kwak, M.-K.
Affiliations
  • Catholic University of Korea (KR)
  • Yeungnam University (KR)
Corresponding author
Kwak, Mi-Kyoung
ORCID
Venue
Toxicology Letters
Publisher
Elsevier BV
Published
2013-03
Volume
218
Issue
1
Pages
39-49
ISSN
0378-4274 (ISSN-L)
DOI
10.1016/j.toxlet.2012.12.026
OpenAlex
W1977032723
Cited by
113
References
58
Citations by year
2026: 3 · 2025: 10 · 2024: 8 · 2023: 8 · 2022: 7 · 2021: 16 · 2020: 6 · 2019: 6 · 2018: 6 · 2017: 10 · 2016: 9 · 2015: 8 · 2014: 9 · 2013: 7
FWCI
4.93
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Toxicology Letters (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Research Foundation of Korea
  • Ministry of Education, Science and Technology (2011-0017977)
  • Catholic University of Korea
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Keywords
Nrf2, aldo-keto reductase, AKR1C1, aldose reductase, AKR1B10, AKR1C2, AKR1C3, Nrf2 target genes, Keap1, sulforaphane, oxidative stress, electrophilic stress, THP-1 cells, CD14+ monocytes, gene expression profiling
MeSH terms
Kelch-Like ECH-Associated Protein 1, Acrolein, Aldehyde Reductase, Enzyme Induction, Gene Expression Regulation, Genetic Markers, Humans, Hydrogen Peroxide, Hydroquinones, Kidney Tubules, Proximal, Leukemia, Monocytic, Acute, Monocytes, Sulfoxides, Thiocyanates, 20-Hydroxysteroid Dehydrogenases, Biomarkers, Isothiocyanates, Oxidative Stress, U937 Cells, Gene Silencing, Intracellular Signaling Peptides and Proteins, NF-E2-Related Factor 2, Gene Knockdown Techniques

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