ArticleAmino acids2014
Upregulation of capacity for glutathione synthesis in response to amino acid deprivation: regulation of glutamate-cysteine ligase subunits.
Article in Amino acids, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 51 citations in OpenAlex.
- Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial.Journal of translational medicine · 2024Trial
- Effects of dietary methionine and cysteine restriction on plasma biomarkers, serum fibroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study.Journal of translational medicine · 2020Trial
- Multi-omics characterization of the skin microbiota reveals the anti-aging roles of Stenotrophomonas maltophilia.Microbiome · 2026Article
- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
- Curcumin Modulation of the Gut-Brain Axis for Neuroinflammation and Metabolic Disorders Prevention and Treatment.Nutrients · 2025Review
- 1,4-dihydroxy quininib activates ferroptosis pathways in metastatic uveal melanoma and reveals a novel prognostic biomarker signature.Cell death discovery · 2024Article
- The Minimum Methionine Requirement for Adults Aged ≥60 Years Is the Same in Males and Females.Nutrients · 2023Article
- Protein Phosphorylation and Redox Status: An as Yet Elusive Dyad in Chronic Lymphocytic Leukemia.Cancers · 2022Review
- A Multi-Omics Approach to Evaluate the Toxicity Mechanisms Associated with Silver Nanoparticles Exposure.Nanomaterials (Basel, Switzerland) · 2022Article
- Ferroptosis and its role in skeletal muscle diseases.Frontiers in molecular biosciences · 2022Review
- Na/H Exchange Regulatory Factor 1 Deficient Mice Show Evidence of Oxidative Stress and Altered Cisplatin Pharmacokinetics.Antioxidants (Basel, Switzerland) · 2021Article
- Glucose Availability Alters Gene and Protein Expression of Several Newly Classified and Putative Solute Carriers in Mice Cortex Cell Culture andFrontiers in cell and developmental biology · 2020Article
- Deficit of mitogen-activated protein kinase phosphatase 1 (DUSP1) accelerates progressive hearing loss.eLife · 2019Article
- Article
- Altered metabolic landscape in IDH-mutant gliomas affects phospholipid, energy, and oxidative stress pathways.EMBO molecular medicine · 2017Article
- Article
- Sub-toxic Ethanol Exposure Modulates Gene Expression and Enzyme Activity of Antioxidant Systems to Provide Neuroprotection in Hippocampal HT22 Cells.Frontiers in physiology · 2016Article
- Oregano Essential Oil Induces SOD1 and GSH Expression through Nrf2 Activation and Alleviates Hydrogen Peroxide-Induced Oxidative Damage in IPEC-J2 Cells.Oxidative medicine and cellular longevity · 2016Article
- A sustained deficiency of mitochondrial respiratory complex III induces an apoptotic cell death through the p53-mediated inhibition of pro-survival activities of the activating transcription factor 4.Cell death & disease · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Using HepG2/C3A cells and MEFs, we investigated whether induction of GSH synthesis in response to sulfur amino acid deficiency is mediated by the decrease in cysteine levels or whether it requires a decrease in GSH levels per se. Both the glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunit mRNA levels were upregulated in response to a lack of cysteine or other essential amino acids, independent of GSH levels. This upregulation did not occur in MEFs lacking GCN2 (general control non-derepressible 2, also known as eIF2α kinase 4) or in cells expressing mutant eIF2α lacking the eIF2α kinase Ser(51) phosphorylation site, indicating that expression of both GCLC and GCLM was mediated by the GCN2/ATF4 stress response pathway. Only the increase in GCLM mRNA level, however, was accompanied by a parallel increase in protein expression, suggesting that the enhanced capacity for GSH synthesis depended largely on increased association of GCLC with its regulatory subunit. Upregulation of both GCLC and GLCM mRNA levels in response to cysteine deprivation was dependent on new protein synthesis, which is consistent with expression of GCLC and GCLM being mediated by proteins whose synthesis depends on activation of the GCN2/ATF4 pathway. Our data suggest that the regulation of GCLC expression may be mediated by changes in the abundance of transcriptional regulators, whereas the regulation of GCLM expression may be mediated by changes in the abundance of mRNA stabilizing or destabilizing proteins. Upregulation of GCLM levels in response to low cysteine levels may serve to protect the cell in the face of a future stress requiring GSH as an antioxidant or conjugating/detoxifying agent.
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Registered trials
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