ArticleThe Biochemical journal2006
Differential regulation of glutamate-cysteine ligase subunit expression and increased holoenzyme formation in response to cysteine deprivation.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
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- Prevention of age-related truncation of γ-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation.Science advances · 2024Article
- Short-term feed restriction induces inflammation and an antioxidant response via cystathionine-β-synthase and glutathione peroxidases in ruminal epithelium from Angus steers.Journal of animal science · 2024Article
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- Effects of Copper Nanoparticles on mRNA and Small RNA Expression in Human Hepatocellular Carcinoma (HepG2) Cells.Journal of nanoscience and nanotechnology · 2021Article
- Activation of NRF2 and ATF4 Signaling by the Pro-Glutathione Molecule I-152, a Co-Drug ofAntioxidants (Basel, Switzerland) · 2021Article
- Carveol a Naturally-Derived Potent and Emerging Nrf2 Activator Protects Against Acetaminophen-Induced Hepatotoxicity.Frontiers in pharmacology · 2020Article
- Thioredoxin Reductase-1 Inhibition Augments Endogenous Glutathione-Dependent Antioxidant Responses in Experimental Bronchopulmonary Dysplasia.Oxidative medicine and cellular longevity · 2019Article
- Targeting Glutamine Metabolism for Cancer Treatment.Biomolecules & therapeutics · 2018Review
- Exercise induced upregulation of glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modifier subunit gene expression in Thoroughbred horses.Asian-Australasian journal of animal sciences · 2017Article
- Nuclear localization of glutamate-cysteine ligase is associated with proliferation in head and neck squamous cell carcinoma.Oncology letters · 2016Article
- t-BHQ Provides Protection against Lead Neurotoxicity via Nrf2/HO-1 Pathway.Oxidative medicine and cellular longevity · 2016Article
- Resveratrol affects the expression of glutamate cysteine ligase in the kidneys of aged rats.Experimental and therapeutic medicine · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
GCL (glutamate-cysteine ligase) is a heterodimer of a GCLC (GCL catalytic subunit) that possesses all of the enzymatic activity and a GCLM (GCL modifier subunit) that alters the K(i) of GCLC for GSH. We hypothesized that the expression of GCLM and the association of GCLM with GCLC were responsible for the apparent increase in GCL activity state observed in the liver of rats fed low-protein diets or in hepatocytes cultured in low-sulphur amino acid-containing medium. Therefore we conducted a series of studies using rats and a human hepatoma (HepG2/C3A) cell line to assess the role of GCLM and holoenzyme formation in the regulation of GCL activity in response to sulphur amino acid intake or availability. Increases in GCL activity in rat liver, as well as in HepG2 cells, were due to the additive effects of changes in the amount of GCLC and the kcat for GCLC. The increase in the kcat for GCLC was associated with increased holoenzyme formation, which was associated with an increase in the molar ratio of GCLM to GCLC. Furthermore, our results indicate that the GCLM level in rat liver is always limiting and that up-regulation of the GCLM level results in increased holoenzyme formation and an increase in the kcat. This is the first report demonstrating that the catalytic efficiency of rat GCL is increased by holoenzyme formation and the first demonstration of differential up-regulation of the GCL subunits in response to cysteine deprivation.
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