ArticleMolecular medicine reports2018
Activation of the KEAP1‑NRF2‑ARE signaling pathway reduces oxidative stress in Hep2 cells.
Article in Molecular medicine reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Overcoming Radiation Resistance: Ferroptosis Induction to Sensitize Solid Tumors to Radiation Therapy.Cancer medicine · 2026Review
- CUL7-mediated KEAP1 ubiquitination promotes the progression of colon cancer via NRF2 signaling.Cell death & disease · 2026Article
- Article
- Subchronic Chlorpyrifos Exposure Induces Thyroid Follicular Cell Pyroptosis to Exacerbate Thyroid Toxicity by Modulating Nrf2/Keap1/NF-κB Pathway in Male Mice.Journal of inflammation research · 2025Article
- A comprehensive survey of warfarin-induced hepatic toxicity using histopathological, biomarker, and molecular evaluation.Heliyon · 2024Article
- Mechanism of Action and Related Natural Regulators of Nrf2 in Nonalcoholic Fatty Liver Disease.Current drug delivery · 2024Review
- Protective effect of short-chain fructo-oligosaccharides from chicory on alcohol-induced injury in GES-1 cells via Keap1/Nrf2 and NLRP3 inflammasome signaling pathways.Frontiers in nutrition · 2024Article
- Effect of RNF113A deficiency on oxidative stress-induced NRF2 pathway.Animal cells and systems · 2024Article
- Mechanisms of mitophagy and oxidative stress in cerebral ischemia-reperfusion, vascular dementia, and Alzheimer's disease.Frontiers in molecular neuroscience · 2024Review
- NOP16 promotes hepatocellular carcinoma progression and triggers EMT through the Keap1-Nrf2 signaling pathway.Technology and health care : official journal of the European Society for Engineering and Medicine · 2024Article
- Effects and Mechanisms of Non-Thermal Plasma-Mediated ROS and Its Applications in Animal Husbandry and Biomedicine.International journal of molecular sciences · 2023Review
- Melatonin attenuates high glucose‑induced endothelial cell pyroptosis by activating the Nrf2 pathway to inhibit NLRP3 inflammasome activation.Molecular medicine reports · 2023Article
- Investigating the functional role of SETD6 in lung adenocarcinoma.BMC cancer · 2023Article
- Natural Nrf2 Inhibitors: A Review of Their Potential for Cancer Treatment.International journal of biological sciences · 2023Review
- Therapeutic Potential of Plant Oxylipins.International journal of molecular sciences · 2022Review
- Article
- Protecting Effect of Bacillus coagulans T242 on HT-29 Cells Against AAPH-Induced Oxidative Damage.Probiotics and antimicrobial proteins · 2022Article
- Evaluation of the role of Nrf2/Keap1 pathway-associated novel mutations and gene expression on antioxidant status in patients with deep vein thrombosis.Experimental and therapeutic medicine · 2020Article
- The Clinicopathological and Prognostic Significance of Nrf2 and Keap1 Expression in Hepatocellular Carcinoma.Cancers · 2020Article
- Stigmasterol alleviates cerebral ischemia/reperfusion injury by attenuating inflammation and improving antioxidant defenses in rats.Bioscience reports · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
At present there are no studies investigating the effects of the kelch‑like ECH‑associated protein 1 (KEAP1)‑nuclear factor erythroid 2‑related factor 2 (NRF2)‑antioxidant response element (ARE) signaling pathway on Hep2 cell line. The present study aimed to investigate this topic through knockdown of the KEAP1 gene. A stable Hep2 cell line specifically silencing the human KEAP1 gene was initially constructed. Hydrogen peroxide (H2O2) was added to the culture medium at various concentrations for various durations to interact with the short hairpin (sh)KEAP1‑transfected Hep2 cells. Subsequently, the gene and protein expression levels of KEAP1, NRF2, NAD(P)H quinone oxidoreductase1 (NQO1) and heme oxygenase 1 (HO1) in experimental and control cells were measured by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. Furthermore, the viability and apoptotic rate of the shKEAP1‑transfected Hep2 cells were detected by a Cell Counting‑Kit 8 assay and flow cytometry, respectively. In the shKEAP1 Hep2 cell line, the mRNA and protein expression levels of NRF2, NQO1 and HO1 were markedly higher compared with the scramble control‑transfected Hep2 and parent Hep2 cell lines. Immunofluorescence staining indicated that NRF2 was primarily located in the cytoplasm of scHep2 and parent Hep2 cell lines, but was present in the nuclei and cytoplasm of the shKEAP1 Hep2 cell line, where it translocates into the nuclei in response to H2O2. Following knockdown of the KEAP1 gene Hep2 cells, the apoptosis rates were 31.8 and 45.3% in scHep2 cells at 0.1 and 0.25 mmol/l H2O2 respectively and 14.1 and 27.9% in shKEAP1 cells. The present study indicated that the KEAP1‑NRF2‑ARE signaling pathway may exhibit an antioxidative effect within Hep2 cells and may be used for clinical treatment of cancer.
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