ArticleMolecular medicine reports2017
Nrf2 mediates the protective effects of homocysteine by increasing the levels of GSH content in HepG2 cells.
Article in Molecular medicine reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Nicotinamide N-Methyltransferase (NNMT) and Liver Cancer: From Metabolic Networks to Therapeutic Targets.Biomolecules · 2025Review
- Effect of Ultra-High Pressure on the Extraction of the Free, Esterified, and Bound Phenolics fromMolecules (Basel, Switzerland) · 2025Article
- HADH suppresses clear cell renal cell carcinoma progression through reduced NRF2-dependent glutathione synthesis.Translational oncology · 2024Article
- Current Insights into the Role of UV Radiation-Induced Oxidative Stress in Melanoma Pathogenesis.International journal of molecular sciences · 2024Review
- The Role of Organosulfur Compounds as Nrf2 Activators and Their Antioxidant Effects.Antioxidants (Basel, Switzerland) · 2022Review
- Nrf2/ARE axis signalling in hepatocyte cellular death.Molecular biology reports · 2022Review
- Hydroxynonenal Causes Hepatocyte Death by Disrupting Lysosomal Integrity in Nonalcoholic Steatohepatitis.Cellular and molecular gastroenterology and hepatology · 2022Article
- Oxidative Stress and 4-hydroxy-2-nonenal (4-HNE): Implications in the Pathogenesis and Treatment of Aging-related Diseases.Journal of immunology research · 2022Review
- The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies.Antioxidants (Basel, Switzerland) · 2020Review
- The NRF2/KEAP1 Axis in the Regulation of Tumor Metabolism: Mechanisms and Therapeutic Perspectives.Biomolecules · 2020Review
- Excess homocysteine upregulates the NRF2-antioxidant pathway in retinal Müller glial cells.Experimental eye research · 2019Article
- Nuclear factor erythroid 2-related factor 2 activation mediates hyperhomocysteinemia-associated lipolysis suppression in adipocytes.Experimental biology and medicine (Maywood, N.J.) · 2018Article
- TheFrontiers in immunology · 2018Article
- Betaine in Inflammation: Mechanistic Aspects and Applications.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homocysteine (Hcy) and glutathione (GSH) are crucial reduction‑oxidation mediators. The underlying mechanisms governing the effects of Hcy on GSH generation in the progression of alcoholic liver disease has so far received little attention. The present study hypothesized that the antioxidant transcriptional factor nuclear factor (erythroid‑derived 2)‑like 2 (Nrf2) may participate in Hcy‑mediated regulation of GSH production in HepG2 human liver cancer cells. MTT assay was used to study the cytotoxicity of homocysteine, western blot analysis and immunofluorescence staining were used to determine the effect of Hcy on Nrf2 expression. Our data demonstrated that HepG2 cells exposed to exogenous levels of Hcy (0‑100 µM) exhibited elevated GSH levels in a concentration‑dependent manner. Furthermore, 4‑hydroxynonenal (4‑HNE)‑induced cell injury was attenuated by Hcy; however, this protective effect was blocked by the GSH‑production inhibitor buthionine sulfoximine. Hcy treatment was able to induce Nrf2 protein expression in HepG2 cells. Treatment with the Nrf2 activator tert‑butylhydroquinone (0‑100 µM) increased GSH expression in a concentration‑dependent manner; however, Nrf2‑siRNA abolished the Hcy‑induced increase in GSH expression and cellular protection in 4‑HNE‑stressed HepG2 cells. In conclusion, the antioxidant transcriptional factor Nrf2 was demonstrated to mediate the Hcy‑induced increase in GSH expression levels and cellular protection in HepG2 cells.
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