Cited by 997Genomics, phytochemicals, and oxidative stressRedox biology and oxidative stressGlutathione Transferases and Polymorphisms

The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index.

Molecular basis of the Keap1–Nrf2 system

Open access

Suzuki, Takafumi, Yamamoto, Masayuki·2015·Free Radical Biology and Medicine

DOI 10.1016/j.freeradbiomed.2015.06.006

Open this paper in CoChat — free account

Abstract

Nrf2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. Nrf2 induces the expression of detoxification and antioxidant enzymes, and Keap1 (Kelch-like ECH-associated protein 1), an adaptor subunit of Cullin 3-based E3 ubiquitin ligase, regulates Nrf2 activity. Keap1 also acts as a sensor for oxidative and electrophilic stresses. Keap1 retains multiple sensor cysteine residues that detect various stress stimuli. Increasing attention has been paid to the roles that Nrf2 plays in the protection of our bodies against drug toxicity and stress-induced diseases. On the other hand, Nrf2 is found to promote both oncogenesis and cancer cell resistance against chemotherapeutic drugs. Thus, although Nrf2 acts to protect our body from deleterious stresses, cancer cells hijack the Nrf2 activity to support their malignant growth. Nrf2 has emerged as a new therapeutic target, and both inducers and inhibitors of Nrf2 are awaited. Studies challenging the molecular basis of the Keap1-Nrf2 system functions are now critically important to improve translational studies of the system. Indeed, recent studies identified cross talk between Nrf2 and other signaling pathways, which provides new insights into the mechanisms by which the Keap1-Nrf2 system serves as a potent regulator of our health and disease.

Integrity signals

Registry

Crossref · 10.1016/j.freeradbiomed.2015.06.006

Cites

84 of 84 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

An Nrf2/Small Maf Heterodimer Mediates the Induction of Phase II Detoxifying Enzyme Genes through Antioxidant Response Elements
Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6943 · Cited by 3,999
Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999) · Genes & Development · doi:10.1101/gad.13.1.76 · Cited by 3,634
Self-citation
The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1
Komatsu, M., Kurokawa, H., Waguri, S., Taguchi, K., Kobayashi, A., Ichimura, Y., Sou, Y.-S., Ueno, I., Sakamoto, A., Tong, K. I., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2021 · Cited by 2,288
Self-citation
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K. H., Yeo, C. J., Calhoun, E. S., et al. (2011) · Nature · doi:10.1038/nature10189 · Cited by 2,277
Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2
Kobayashi, A., Kang, M.-I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K., & Yamamoto, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7130-7139.2004 · Cited by 2,224
The Nrf2 regulatory network provides an interface between redox and intermediary metabolism
Hayes, J. D., & Dinkova‐Kostova, A. T. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.002 · Cited by 2,210
Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants
Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., & Talalay, P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172398899 · Cited by 1,947
Self-citation
Nrf2–Keap1 defines a physiologically important stress response mechanism
Motohashi, H., & Yamamoto, M. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.09.003 · Cited by 1,725
Self-citation
Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress
Zhang, D. D., & Hannink, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.8137-8151.2003 · Cited by 1,480
Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming
Mitsuishi, Y., Taguchi, K., Kawatani, Y., Shibata, T., Nukiwa, T., Aburatani, H., Yamamoto, M., & Motohashi, H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.05.016 · Cited by 1,395
Self-citation

Show all 84 references

Sorted by citations

Items 101–200 of 997

Traditional Chinese medicine Gegen Qinlian decoction ameliorates irinotecan chemotherapy-induced gut toxicity in mice
Wu, Y., Wang, D., Yang, X., Fu, C., Zou, L., & Zhang, J. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.11.095 · Cited by 92
4-Octyl Itaconate Activates Nrf2 Signaling to Inhibit Pro-Inflammatory Cytokine Production in Peripheral Blood Mononuclear Cells of Systemic Lupus Erythematosus Patients
Tang, C., Wang, X., Xie, Y., Cai, X., Yu, N. H., Hu, Y., & Zheng, Z. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000495400 · Cited by 91
6-Gingerol ameliorates sepsis-induced liver injury through the Nrf2 pathway
Hong, M., Hu, L., Zhang, Y.-X., Xu, Y., Liu, X., He, P., & Jia, Y. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106196 · Cited by 90
Nrf2 activator, sulforaphane ameliorates autism-like symptoms through suppression of Th17 related signaling and rectification of oxidant-antioxidant imbalance in periphery and brain of BTBR T+tf/J mice
Nadeem, A., Ahmad, S. F., Al-Harbi, N. O., Attia, S. M., Bakheet, S. A., Ibrahim, K. E., Alqahtani, F., & Alqinyah, M. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.02.031 · Cited by 92
Involvement of Nrf2 in Ocular Diseases
Batliwala, S. Y., Xavier, C., Liu, Y., Wu, H., & Pang, I.-H. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/1703810 · Cited by 93
Neuroprotection by glucose‐6‐phosphate dehydrogenase and the pentose phosphate pathway
Tang, B. L. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29004 · Cited by 85
Nrf2: a dark horse in doxorubicin-induced cardiotoxicity
Zhao, X., Tian, Z., Sun, M., & Dong, D. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01565-0 · Cited by 94
The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?
Glorieux, C., Enriquez-Lara, C., González, C. D., Aguirre-Martínez, G. V., & Calderón, P. B. (2024) · Antioxidants · doi:10.3390/antiox13010070 · Cited by 97
Bach1 differentially regulates distinct Nrf2-dependent genes in human venous and coronary artery endothelial cells adapted to physiological oxygen levels
Chapple, S. J., Keeley, T. P., Mastronicola, D., Arno, M. J., Vizcay‐Barrena, G., Fleck, R. A., Siow, R. C. M., & Mann, G. E. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.12.013 · Cited by 87
New insights into the role of the Nrf2 signaling pathway in green tea catechin applications
Talebi, M., Talebi, M., Farkhondeh, T., Mishra, G., İlgün, S., & Samarghandian, S. (2021) · Phytotherapy Research · doi:10.1002/ptr.7033 · Cited by 90
Small molecules inhibiting Keap1-Nrf2 protein-protein interactions: A novel approach to activate Nrf2 function
Zhuang, C., Wu, Z., Xing, C., & Miao, Z. (2017) · MedChemComm · doi:10.1039/c6md00500d · Cited by 84
The Effects of Antioxidants from Natural Products on Obesity, Dyslipidemia, Diabetes and Their Molecular Signaling Mechanism
Khutami, C., Sumiwi, S. A., Ikram, N. K. K., & Muchtaridi, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042056 · Cited by 83
Recent progress in Keap1-Nrf2 protein-protein interaction inhibitors
Mou, Y., Wen, S., Li, Y., Gao, X., Zhang, X., & Jiang, Z. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112532 · Cited by 85
Ginsenoside Rg1 prevents bone marrow mesenchymal stem cell senescence via NRF2 and PI3K/Akt signaling
Wang, Z., Wang, L., Jiang, R., Li, C., Chen, X., Xiao, H., Hou, J., Hu, L., Huang, C., & Wang, Y. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.08.007 · Cited by 84
Long-term exposure to PM2.5 aggravates pulmonary fibrosis and acute lung injury by disrupting Nrf2-mediated antioxidant function
Zhao, C. N., Pu, W., Wazir, J., Jin, X., Wei, L., Song, S., Su, Z., Li, J., Deng, Y., & Wang, H. (2022) · Environmental Pollution · doi:10.1016/j.envpol.2022.120017 · Cited by 85
NRF2 facilitates breast cancer cell growth via HIF1ɑ-mediated metabolic reprogramming
Zhang, H., Du, G.-Y., Zhang, Z.-G., Zhou, Z., Sun, H., Yu, X., Shi, Y., Xiong, D.-N., Li, H., & Huang, Y. (2017) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.12.016 · Cited by 83
Oxidant-specific biomarkers of oxidative stress. Association with atherosclerosis and implication for antioxidant effects
Niki, E. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.04.001 · Cited by 84
The mycosporine-like amino acids porphyra-334 and shinorine are antioxidants and direct antagonists of Keap1-Nrf2 binding
Gaćeša, R., Lawrence, K. P., Georgakopoulos, N., Yabe, K., Dunlap, W. C., Barlow, D. J., Wells, G., Young, A. R., & Long, P. F. (2018) · Biochimie · doi:10.1016/j.biochi.2018.07.020 · Cited by 83
Covalent modification of Keap1 at Cys77 and Cys434 by pubescenoside a suppresses oxidative stress-induced NLRP3 inflammasome activation in myocardial ischemia-reperfusion injury
Cheng, Y., Cheng, L., Gao, X., Chen, S., Wu, P., Wang, C., & Liu, Z. (2020) · Theranostics · doi:10.7150/thno.48436 · Cited by 81
Autophagy Inhibition Plays a Protective Role in Ferroptosis Induced by Alcohol via the p62–Keap1–Nrf2 Pathway
Zhao, Y., Lü, J., Mao, A., Zhang, R., & Guan, S. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.1c03751 · Cited by 81
High glucose concentrations induce oxidative stress by inhibiting Nrf2 expression in rat Müller retinal cells in vitro
Albert-Garay, J. S., Riesgo‐Escovar, J. R., & Salceda, R. (2022) · Scientific Reports · doi:10.1038/s41598-022-05284-x · Cited by 82
Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, and miR-155 Expression and Switches to Mox Phenotype through Activating Extracellular Signal-Regulated Kinase 1/2–Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway in Murine Microglial Cells
Eren, E., Tüfekçi, K. U., Isci, K. B., Tastan, B., Genç, K., & Genç, Ş. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00036 · Cited by 84
SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling
Gong, Y.-Q., Huang, W., Li, K., Liu, Y.-Y., Cao, G.-F., Cao, C., & Jiang, Q. L. (2016) · Oncotarget · doi:10.18632/oncotarget.11164 · Cited by 81
Cerebrovascular and Neurological Disorders: Protective Role of NRF2
Sivandzade, F., Bhalerao, A., & Cucullo, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143433 · Cited by 79
Ursolic and Oleanolic Acids Induce Mitophagy in A549 Human Lung Cancer Cells
Castrejón-Jiménez, N. S., Leyva-Paredes, K., Baltierra‐Uribe, S. L., Castillo-Cruz, J., Campillo-Navarro, M., Hernández‐Pérez, A. D., Luna‐Angulo, A. B., Chacón‐Salinas, R., Coral‐Vázquez, R. M., Estrada‐García, I., et al. (2019) · Molecules · doi:10.3390/molecules24193444 · Cited by 80
Association of Zinc Deficiency with Development of CVD Events in Patients with CKD
Nakatani, S., Mori, K., Shoji, T., & Emoto, M. (2021) · Nutrients · doi:10.3390/nu13051680 · Cited by 79
HCV and Oxidative Stress: Implications for HCV Life Cycle and HCV‐Associated Pathogenesis
Medvedev, R., Ploen, D., & Hildt, E. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/9012580 · Cited by 81
Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus
Suzuki, T., Seki, S., Hiramoto, K., Naganuma, E., Kobayashi, E. H., Yamaoka, A., Baird, L., Takahashi, N., Sato, H., & Yamamoto, M. P. (2017) · Nature Communications · doi:10.1038/ncomms14577 · Cited by 78
Self-citation
Discovery of a head-to-tail cyclic peptide as the Keap1-Nrf2 protein-protein interaction inhibitor with high cell potency
Lu, M., Jiao, Q., Liu, T., Tan, S.-J., Zhou, H.-S., You, Q., & Jiang, Z. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.10.052 · Cited by 83
l ‐Methionine activates Nrf2‐ARE pathway to induce endogenous antioxidant activity for depressing ROS‐derived oxidative stress in growing rats
Wang, Z., Liang, M., Li, H., Cai, L., He, H., Wu, Q., & Yang, L. (2019) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.9757 · Cited by 79
Cerevisterol Alleviates Inflammation via Suppression of MAPK/NF-κB/AP-1 and Activation of the Nrf2/HO-1 Signaling Cascade
Alam, M. B., Chowdhury, N. S., Sohrab, M. H., Rana, M. S., Hasan, C. M., & Lee, S. (2020) · Biomolecules · doi:10.3390/biom10020199 · Cited by 79
Signals from the Niche: Insights into the Role of IGF-1 and IL-6 in Modulating Skeletal Muscle Fibrosis
Forcina, L., Miano, C., Scicchitano, B. M., & Musarò, A. (2019) · Cells · doi:10.3390/cells8030232 · Cited by 82
Neurodegeneration by oxidative stress: a review on prospective use of small molecules for neuroprotection
Singh, E., & Giles, D. (2020) · Molecular Biology Reports · doi:10.1007/s11033-020-05354-1 · Cited by 80
Particulate matter and the airway epithelium: the special case of the underground?
Cooper, D. M., & Loxham, M. (2019) · European Respiratory Review · doi:10.1183/16000617.0066-2019 · Cited by 80
miRNA-141 attenuates UV-induced oxidative stress via activating Keap1-Nrf2 signaling in human retinal pigment epithelium cells and retinal ganglion cells
Cheng, L., Li, K., Yi, N., Li, X., Wang, F., Xue, B., Pan, Y.-S., Yao, J., Jiang, Q. L., & Wu, Z. (2017) · Oncotarget · doi:10.18632/oncotarget.14489 · Cited by 77
Nrf2-regulated redox signaling in brain endothelial cells adapted to physiological oxygen levels: Consequences for sulforaphane mediated protection against hypoxia-reoxygenation
Warpsinski, G., Smith, M. J., Srivastava, S., Keeley, T. P., Siow, R. C. M., Fraser, P. A., & Mann, G. E. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101708 · Cited by 81
The effect of oxidized phospholipids on phenotypic polarization and function of macrophages
Serbulea, V., DeWeese, D. E., & Leitinger, N. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.02.035 · Cited by 79
CX3CR1-deficient microglia shows impaired signalling of the transcription factor NRF2: Implications in tauopathies
Castro-Sánchez, S., García-Yagüe, Á. J., Kügler, S., & Lastres-Becker, I. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101118 · Cited by 76
Total Glycosides of Cistanche deserticola Promote Neurological Function Recovery by Inducing Neurovascular Regeneration via Nrf-2/Keap-1 Pathway in MCAO/R Rats
Wang, F., Li, R., Tu, P., Chen, J., Zeng, K., & Jiang, Y. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00236 · Cited by 75
Regulation of Keap1–Nrf2 signaling: The role of epigenetics
Cheng, D., Wu, R., Guo, Y., & Kong, A. T. (2016) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2016.10.008 · Cited by 75
The long non-coding RNA MALAT1 activates Nrf2 signaling to protect human umbilical vein endothelial cells from hydrogen peroxide
Zeng, R., Zhang, R., Song, X., Ni, L., Lai, Z., Liu, C., & Ye, W. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.12.105 · Cited by 75
Dimethyl itaconate protects against fungal keratitis by activating the Nrf2/HO‐1 signaling pathway
Gu, L., Lin, J., Wang, Q., Cui, L., Peng, X., Fan, Y., Lu, C., Lin, H., Niu, Y., Zhu, G., et al. (2020) · Immunology and Cell Biology · doi:10.1111/imcb.12316 · Cited by 74
Humanin regulates oxidative stress in the ovaries of polycystic ovary syndrome patients via the Keap1/Nrf2 pathway
Wang, Y., Li, N., Zeng, Z., Tang, L., Zhao, S., Zhou, F., Zhou, L., Xia, W., Zhu, C., & Rao, M. (2020) · Molecular Human Reproduction · doi:10.1093/molehr/gaaa081 · Cited by 74
Exosomes Derived from Baicalin‐Pretreated Mesenchymal Stem Cells Alleviate Hepatocyte Ferroptosis after Acute Liver Injury via the Keap1‐NRF2 Pathway
Zhao, S., Huang, M., Yan, L., Zhang, H., Shi, C., Liu, J., Shousong, Z., Liu, H., & Wang, B. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/8287227 · Cited by 74
Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via inhibiting methylation of the keap1 gene promoter region
Liu, X., Sun, C., Liu, B., Jin, X., Li, P., Zheng, X., Zhao, T., Li, F., & Li, Q. (2016) · Oncotarget · doi:10.18632/oncotarget.8403 · Cited by 74
Concerted redox modulation by sulforaphane alleviates diabetes and cardiometabolic syndrome
Patel, B., Mann, G. E., & Chapple, S. J. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.02.004 · Cited by 77
Opposing effects of Nrf2 and Nrf2-activating compounds on the NLRP3 inflammasome independent of Nrf2-mediated gene expression
Garstkiewicz, M., Strittmatter, G. E., Grossi, S., Sand, J., Fenini, G., Werner, S., French, L. E., & Beer, H. (2017) · European Journal of Immunology · doi:10.1002/eji.201646665 · Cited by 72
Nrf2 knockout altered brain iron deposition and mitigated age-related motor dysfunction in aging mice
Han, K., Jin, X., Guo, X., Cao, G., Tian, S., Song, Y., Zuo, Y., Yu, P., Gao, G., & Chang, Y. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.11.019 · Cited by 73
The Regulation of NFE2L2 (NRF2) Signalling and Epithelial-to-Mesenchymal Transition in Age-Related Macular Degeneration Pathology
Hyttinen, J. M. T., Kannan, R., Felszeghy, S., Niittykoski, M., Salminen, A., & Kaarniranta, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225800 · Cited by 70
Four-octyl itaconate activates Nrf2 cascade to protect osteoblasts from hydrogen peroxide-induced oxidative injury
Zheng, Y., Chen, Z., She, C., Lin, Y., Yuan, H., Shi, L., Zhang, Y., Cao, P., & Xu, X. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02987-9 · Cited by 71
Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling
Slominski, R. M., Kim, T., Janjetović, Z., Brożyna, A. A., Podgórska, E., Dixon, K. M., Mason, R. S., Tuckey, R. C., Sharma, R., Crossman, D. K., et al. (2024) · Cancers · doi:10.3390/cancers16122262 · Cited by 79
Redox stress and signaling during vertebrate embryonic development: Regulation and responses
Timme‐Laragy, A. R., Hahn, M. E., Hansen, J. M., Rastogi, A., & Roy, M. A. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.09.019 · Cited by 76
Melatonin alleviates aluminium chloride-induced immunotoxicity by inhibiting oxidative stress and apoptosis associated with the activation of Nrf2 signaling pathway
Yu, H., Zhang, J., Ji, Q., Yu, K., Wang, P., Song, M., Cao, Z., Zhang, X., & Li, Y. (2019) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2019.01.095 · Cited by 70
Protective Effect of Lactobacillus rhamnosus GG and its Supernatant against Myocardial Dysfunction in Obese Mice Exposed to Intermittent Hypoxia is Associated with the Activation of Nrf2 Pathway
Xu, H. M., Wang, J., Cai, J., Feng, W., Wang, Y., Liu, Q., & Cai, L. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.36465 · Cited by 70
An insight into role of amino acids as antioxidants via NRF2 activation
Egbujor, M. C., Olaniyan, O. T., Emeruwa, C. N., Saha, S., Saso, L., & Tucci, P. (2024) · Amino Acids · doi:10.1007/s00726-024-03384-8 · Cited by 77
The NRF-2/HO-1 Signaling Pathway: A Promising Therapeutic Target for Metabolic Dysfunction-Associated Steatotic Liver Disease
Li, N., Hao, L., Li, S., Deng, J., Yu, F., Zhang, J., Nie, A., & Hu, X. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s490418 · Cited by 74
Cellular redox, cancer and human papillomavirus
Cruz‐Gregorio, A., Manzo-Merino, J., & Lizano, M. (2018) · Virus Research · doi:10.1016/j.virusres.2018.01.003 · Cited by 71
p62/SQSTM1 and Nrf2 are essential for exercise‐mediated enhancement of antioxidant protein expression in oxidative muscle
Yamada, M., Iwata, M., Warabi, E., Oishi, H., Lira, V. A., & Okutsu, M. (2019) · The FASEB Journal · doi:10.1096/fj.201900133r · Cited by 63
Maresin1 Suppresses High-Glucose-Induced Ferroptosis in Osteoblasts via NRF2 Activation in Type 2 Diabetic Osteoporosis
Zhang, Z., Ji, C., Wang, Y., Liu, S., Wang, M., Xu, X., & Zhang, D. (2022) · Cells · doi:10.3390/cells11162560 · Cited by 71
Mitochondrial energetics is impaired in very long-chain acyl-CoA dehydrogenase deficiency and can be rescued by treatment with mitochondria-targeted electron scavengers
Seminotti, B., Leipnitz, G., Karunanidhi, A., Kochersperger, C., Roginskaya, V. Y., Basu, S., Wang, Y., Wipf, P., Houten, B. V., Mohsen, A.-W. A., et al. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy403 · Cited by 69
Small molecules targeting protein–protein interactions for cancer therapy
Wu, D., Li, Y., Zheng, L., Xiao, H., Ouyang, L., Wang, G., & Sun, Q. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.05.035 · Cited by 71
Glycocalyx sialic acids regulate Nrf2-mediated signaling by fluid shear stress in human endothelial cells
Psefteli, P., Kitscha, P., Vizcay‐Barrena, G., Fleck, R. A., Chapple, S. J., Mann, G. E., Fowler, M. I., & Siow, R. C. M. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101816 · Cited by 67
The Pleiotropic Role of the KEAP1/NRF2 Pathway in Cancer
Wu, W., & Papagiannakopoulos, T. Y. (2020) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030518-055627 · Cited by 70
Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus
Mihaylova, V. T., Kong, Y., Fedorova, O., Sharma, L., Dela Cruz, C. S., Pyle, A. M., Iwasaki, A., & Foxman, E. F. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.033 · Cited by 59
Inhibition of Nrf2 degradation alleviates age-related osteoporosis induced by 1,25-Dihydroxyvitamin D deficiency
Yang, R., Zhang, J., Li, J., Qin, R., Chen, J., Wang, R., Goltzman, D., & Miao, D. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.12.010 · Cited by 67
Reprogramming of Energy Metabolism in Response to Radiotherapy in Head and Neck Squamous Cell Carcinoma
Cruz‐Gregorio, A., Martínez-Ramírez, I., Pedraza‐Chaverrí, J., & Lizano, M. (2019) · Cancers · doi:10.3390/cancers11020182 · Cited by 67
Pterostilbene Decreases the Antioxidant Defenses of Aggressive Cancer Cells In Vivo : A Physiological Glucocorticoids- and Nrf2-Dependent Mechanism
Benlloch, M., Obrador, E., Vallés, S. L., Rodríguez, M. L., Sirerol, J. A., Alcácer, J., Pellicer, J. A., Palmer, R. S., Cerdá, C., Sáez, G. T., et al. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6437 · Cited by 68
The molecular mechanism of Nrf2-Keap1 signaling pathway in the antioxidant defense response induced by BaP in the scallop Chlamys farreri
Wang, H., Pan, L., Xu, R., Si, L., & Zhang, X. (2019) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2019.06.006 · Cited by 65
Biological and therapeutic activities of thymoquinone: Focus on the Nrf2 signaling pathway
Talebi, M., Talebi, M., Farkhondeh, T., & Samarghandian, S. (2020) · Phytotherapy Research · doi:10.1002/ptr.6905 · Cited by 68
Deoxynivalenol exposure induces liver damage in mice: Inflammation and immune responses, oxidative stress, and protective effects of Lactobacillus rhamnosus GG
Bai, Y., Ma, K., Li, J., Li, J., Bi, C., & Shan, A. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112514 · Cited by 65
Modulation of Nrf2/HO-1 by Natural Compounds in Lung Cancer
Ghareghomi, S., Moosavi-Movahedi, F., Saso, L., Habibi-Rezaei, M., Khatibi, A., Hong, J., & Moosavi-Movahedi, A. (2023) · Antioxidants · doi:10.3390/antiox12030735 · Cited by 49
Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin
Deck, L. M., Hunsaker, L. A., Jagt, T. A. V., Whalen, L. J., Royer, R. E., & Jagt, D. L. V. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.11.048 · Cited by 65
Pelargonidin Modulates Keap1/Nrf2 Pathway Gene Expression and Ameliorates Citrinin-Induced Oxidative Stress in HepG2 Cells
Babu, G. R. S., Anand, T., Ilaiyaraja, N., Khanum, F., & Gopalan, N. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00868 · Cited by 65
Potent Natural Antioxidant Carveol Attenuates MCAO-Stress Induced Oxidative, Neurodegeneration by Regulating the Nrf-2 Pathway
Malik, I., Shah, F. A., Ali, T., Tan, Z., Alattar, A., Ullah, N., Khan, A., Alshaman, R., & Li, S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00659 · Cited by 63
The NRF2-LOC344887 signaling axis suppresses pulmonary fibrosis
Liu, P., Luo, G., Dodson, M. B., Schmidlin, C. J., Wei, Y., Kerimoğlu, B., Ooi, A., Chapman, E., Garcia, J. G. N., & Zhang, D. D. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101766 · Cited by 63
Hormetic and regulatory effects of lipid peroxidation mediators in pancreatic beta cells
Maulucci, G., Daniel, B., Cohen, O., Avrahami, Y., & Sasson, S. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.03.001 · Cited by 63
Nrf2/Keap1 system regulates vascular smooth muscle cell apoptosis for vascular homeostasis: role in neointimal formation after vascular injury
Ashino, T., Yamamoto, M. P., & Numazawa, S. (2016) · Scientific Reports · doi:10.1038/srep26291 · Cited by 63
Self-citation
The role of Nrf2-Keap1 signaling pathway in the antioxidant defense response induced by PAHs in the calm Ruditapes philippinarum
Wang, H., Pan, L., Si, L., & Miao, J. (2018) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2018.06.030 · Cited by 63
Basic Concepts on the Role of Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) in Age-Related Diseases
Francisqueti‐Ferron, F. V., Ferron, A. J. T., Garcia, J. L., Silva, C. C. V. D. A., Costa, M. R., Gregolin, C. S., Moreto, F., Ferreira, A. L. A., Minatel, I. O., & Corrêa, C. R. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133208 · Cited by 62
Novel hepatoprotective peptides derived from protein hydrolysates of mealworm (Tenebrio molitor)
Cho, H.-R., & Lee, S. (2020) · Food Research International · doi:10.1016/j.foodres.2020.109194 · Cited by 62
Plants derived therapeutic strategies targeting chronic respiratory diseases: Chemical and immunological perspective
Prasher, P., Sharma, M., Mehta, M., Paudel, K. R., Satija, S., Chellappan, D. K., Dureja, H., Gupta, G., Tambuwala, M. M., Negi, P., et al. (2020) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2020.109125 · Cited by 62
Bamboo Leaf Flavonoids Extracts Alleviate Oxidative Stress in HepG2 Cells via Naturally Modulating Reactive Oxygen Species Production and Nrf2-Mediated Antioxidant Defense Responses.
Yu, Y., Li, Z., Cao, G.-T., Huang, S., & Yang, H.-S. (2019) · Journal of Food Science · doi:10.1111/1750-3841.14609 · Cited by 55
Effects of the Nrf2 Protein Modulator Salvianolic Acid A Alone or Combined with Metformin on Diabetes-associated Macrovascular and Renal Injury
Wu, P., Yan, Y., Ma, L., Hou, B., He, Y., Zhang, L., Niu, Z., Song, J.-K., Pang, X.-C., Yang, X., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.712703 · Cited by 63
NRF2 transcriptionally activates the heat shock factor 1 promoter under oxidative stress and affects survival and migration potential of MCF7 cells
Paul, S., Ghosh, S., Mandal, S., Sau, S., & Pal, M. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.003376 · Cited by 61
Nrf2 promotes esophageal squamous cell carcinoma (ESCC) resistance to radiotherapy through the CaMKIIα-associated activation of autophagy
Xia, D., Zhang, X., Ma, Y., Zhao, Z., Zhao, R., & Wang, Y. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00456-6 · Cited by 63
PARK7 promotes repair in early steroid-induced osteonecrosis of the femoral head by enhancing resistance to stress-induced apoptosis in bone marrow mesenchymal stem cells via regulation of the Nrf2 signaling pathway
Zhang, F., Yan, Y., Peng, W., Wang, L., Wang, T., Xie, Z., Luo, H., Zhang, J., & Dong, W. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04226-1 · Cited by 58
Oxidative stress as a culprit in diabetic kidney disease
Su, S., Ma, Z., Wu, H., Xu, Z., & Yi, H. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121661 · Cited by 62
Expected and Unexpected Effects of Pharmacological Antioxidants
Tyuryaeva, I. I., & Lyublinskaya, O. G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119303 · Cited by 71
HIV-Tat Induces the Nrf2/ARE Pathway through NMDA Receptor-Elicited Spermine Oxidase Activation in Human Neuroblastoma Cells
Mastrantonio, R., Cervelli, M., Pietropaoli, S., Mariottini, P., Colasanti, M., & Persichini, T. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149802 · Cited by 60
Curcumin alleviates liver oxidative stress in type 1 diabetic rats
Xie, Z., Wu, B., Shen, G., Li, X., & Wu, Q. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7911 · Cited by 60
Jmjd3 regulates inflammasome activation and aggravates DSS‐induced colitis in mice
Huang, M., Wang, Q., Long, F., Di, Y., Wang, J., Zhu, Y. Z., & Liu, X. (2020) · The FASEB Journal · doi:10.1096/fj.201902200rr · Cited by 59
NRF2 in human neoplasm: Cancer biology and potential therapeutic target
Liu, Y., Lang, F., & Yang, C. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107664 · Cited by 61
NFE2L2/NRF2 Activity Is Linked to Mitochondria and AMP-Activated Protein Kinase Signaling in Cancers Through miR-181c/Mitochondria-Encoded Cytochrome c Oxidase Regulation
Jung, K.-A., Lee, S., & Kwak, M. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6797 · Cited by 60
CKIP-1 affects the polyubiquitination of Nrf2 and Keap1 via mediating Smurf1 to resist HG-induced renal fibrosis in GMCs and diabetic mice kidneys
Gong, W., Chen, Z., Zou, Y., Zhang, L., Huang, J., Liu, P., & Huang, H. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.12.013 · Cited by 59
Post-Treatment of Synthetic Polyphenolic 1,3,4 Oxadiazole Compound A3, Attenuated Ischemic Stroke-Induced Neuroinflammation and Neurodegeneration
Alvi, A. M., Kury, L. T. A., Ijaz, M. U., Shah, F. A., Khan, M. T., Sheikh, A. S., Nadeem, H., Khan, A., Zeb, A., & Li, S. (2020) · Biomolecules · doi:10.3390/biom10060816 · Cited by 58
Nrf2 promotes mutant K-ras/p53-driven pancreatic carcinogenesis
Hamada, S., Taguchi, K., Masamune, A., Yamamoto, M. P., & Shimosegawa, T. (2017) · Carcinogenesis · doi:10.1093/carcin/bgx043 · Cited by 58
Self-citation
Fish Skin Gelatin Hydrolysate Production by Ginger Powder Induces Glutathione Synthesis To Prevent Hydrogen Peroxide Induced Intestinal Oxidative Stress via the Pept1-p62-Nrf2 Cascade
Zheng, L., Wei, H., Yu, H., Xing, Q., Zou, Y., Zhou, Y., & Peng, J. (2018) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b02840 · Cited by 58
Hepatic Autophagy Deficiency Compromises Farnesoid X Receptor Functionality and Causes Cholestatic Injury
Khambu, B., Li, T., Yan, S., Yu, C., Chen, X., Goheen, M. P., Li, Y., Lin, J., Cummings, O. W., Lee, Y. A., et al. (2018) · Hepatology · doi:10.1002/hep.30407 · Cited by 58
Astragaloside IV Exerts a Myocardial Protective Effect against Cardiac Hypertrophy in Rats, Partially via Activating the Nrf2/HO-1 Signaling Pathway
Nie, P., Meng, F., Zhang, J., Wei, X., & Shen, C. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/4625912 · Cited by 58
GSTZ1‐1 Deficiency Activates NRF2/IGF1R Axis in HCC via Accumulation of Oncometabolite Succinylacetone
Yang, F., Li, J., Deng, H., Wang, Y., Lei, C., Wang, Q., Jin, X., Liang, L., Xia, J. L., Pan, X., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2019101964 · Cited by 56

Authors: Suzuki, T., & Yamamoto, M.
Affiliations: Tohoku University (JP)
Corresponding author: Yamamoto, Masayuki
ORCID: Suzuki, Takafumi
Yamamoto, Masayuki
Venue: Free Radical Biology and Medicine
Publisher: Elsevier BV
Published: 2015-11
Volume: 88
Issue: Pt B
Pages: 93-100
ISSN: 0891-5849 (ISSN-L)
DOI: 10.1016/j.freeradbiomed.2015.06.006
OpenAlex: W952491933
Cited by: 995
References: 84
Citations by year: 2026: 62 · 2025: 89 · 2024: 83 · 2023: 102 · 2022: 116 · 2021: 104 · 2020: 118 · 2019: 88 · 2018: 78 · 2017: 82 · 2016: 62 · 2015: 10
FWCI: 7.53
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (am, 360 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Free Radical Biology and Medicine (acceptedVersion)
PubMed (publishedVersion)
Funders: Ministry of Education, Culture, Sports, Science and Technology
Japan Science and Technology Agency
Japan Society for the Promotion of Science (26460354, 2611010, 24249015, 25112502)
Takeda Science Foundation
Naito Foundation
Core Research for Evolutional Science and Technology
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: Keap1, Nrf2, oxidative stress sensing, electrophilic stress, chemoresistance, carcinogenesis, Nrf2 inhibitors, Nrf2 inducers, therapeutic target
MeSH terms: Animals, Humans, Signal Transduction, Intracellular Signaling Peptides and Proteins, NF-E2-Related Factor 2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Molecular basis of the Keap1–Nrf2 system

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks