ArticleFree radical biology & medicine2009
Distinct Nrf1/2-independent mechanisms mediate As 3+-induced glutamate-cysteine ligase subunit gene expression in murine hepatocytes.
Article in Free radical biology & medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- A Systematic Review of the Various Effect of Arsenic on Glutathione Synthesis In Vitro and In Vivo.BioMed research international · 2020Pooled it
- Distinct Interactions of Arsenite and Cadmium with Metal Homeostasis and the Cellular Stress Response in Human Bronchial Epithelial Cells.International journal of molecular sciences · 2026Article
- Arsenite-Mediated Transcriptional Regulation of Glutathione Synthesis in Mammalian Primary Cortical Astrocytes.International journal of molecular sciences · 2025Article
- Mechanism study on the attenuation of cerebral ischemia-reperfusion injury by LBP extract through regulation of SIRT1/PGC-1α axis.Translational neuroscience · 2025Article
- Unveiling the multifaceted pathogenesis and therapeutic drugs of Alzheimer's disease: A comprehensive review.Heliyon · 2024Review
- Natural Dietary Compounds in the Treatment of Arsenic Toxicity.Molecules (Basel, Switzerland) · 2022Review
- The mechanisms of ferroptosis and its role in alzheimer's disease.Frontiers in molecular biosciences · 2022Review
- Arsenic co-carcinogenesis: Inhibition of DNA repair and interaction with zinc finger proteins.Seminars in cancer biology · 2021Review
- Risk assessment of low arsenic exposure using biomarkers of oxidative and genotoxic stress in a piscine model.Ecotoxicology (London, England) · 2019Article
- Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress.Toxicology and applied pharmacology · 2015Article
- Article
- Long-term dietary exposure to low concentration of dichloroacetic acid promoted longevity and attenuated cellular and functional declines in aged Drosophila melanogaster.Age (Dordrecht, Netherlands) · 2014Article
- Glutathione synthesis.Biochimica et biophysica acta · 2013Review
- Low-level domoic acid protects mouse cerebellar granule neurons from acute neurotoxicity: role of glutathione.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- A semi-mechanistic integrated toxicokinetic-toxicodynamic (TK/TD) model for arsenic(III) in hepatocytes.Journal of theoretical biology · 2013Article
- A synthetic chalcone as a potent inducer of glutathione biosynthesis.Journal of medicinal chemistry · 2012Article
- Bisphenol A effect on glutathione synthesis and recycling in testicular Sertoli cells.Journal of endocrinological investigation · 2011Article
- Long isoforms of NRF1 contribute to arsenic-induced antioxidant response in human keratinocytes.Environmental health perspectives · 2011Article
- Arsenite causes down-regulation of Akt and c-Fos, cell cycle dysfunction and apoptosis in glutathione-deficient cells.Journal of cellular biochemistry · 2010Article
- Enhanced glutathione biosynthetic capacity promotes resistance to As3+-induced apoptosis.Toxicology letters · 2010Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Trivalent arsenite (As(3+)) is a known human carcinogen that is also capable of inducing apoptotic cell death. Increased production of reactive oxygen species is thought to contribute to both the carcinogenic and the cytotoxic effects of As(3+). Glutathione (GSH) constitutes a vital cellular defense mechanism against oxidative stress. The rate-limiting enzyme in GSH biosynthesis is glutamate-cysteine ligase (GCL), a heterodimeric holoenzyme composed of a catalytic (GCLC) and a modifier (GCLM) subunit. In this study, we demonstrate that As(3+) coordinately upregulates Gclc and Gclm mRNA levels in a murine hepatocyte cell line resulting in increased GCL subunit protein expression, holoenzyme formation, and activity. As(3+) increased the rate of transcription of both the Gclm and the Gclc genes and induced the posttranscriptional stabilization of Gclm mRNA. The antioxidant N-acetylcysteine abolished As(3+)-induced Gclc expression and attenuated induction of Gclm. As(3+) induction of Gclc and Gclm was also differentially regulated by the MAPK signaling pathways and occurred independent of the Nrf1/2 transcription factors. These findings demonstrate that distinct transcriptional and posttranscriptional mechanisms mediate the coordinate induction of the Gclc and Gclm subunits of GCL in response to As(3+) and highlight the potential importance of the GSH antioxidant defense system in regulating As(3+)-induced responses in hepatocytes.
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