Genomes and Genes
Gene Symbol: Gclc
Description: glutamate-cysteine ligase, catalytic subunit
Alias: D9Wsu168e, GLCL-H, Ggcs-hs, Glclc, glutamate--cysteine ligase catalytic subunit, GCS heavy chain, gamma GCS-HS, gamma-ECS, gamma-glutamylcysteine synthetase heavy subunit
- Mechanisms of gamma-glutamylcysteine ligase regulationDikran Toroser
Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089 9121, USA
Biochim Biophys Acta 1760:233-44. 2006..Results of this study suggest that mechanisms of modulation of eukaryotic GCL enzymes may include specific binding of ligands such as pyridine dinucleotide phosphates and reversible protein phosphorylation...
- Knockout of the mouse glutamate cysteine ligase catalytic subunit (Gclc) gene: embryonic lethal when homozygous, and proposed model for moderate glutathione deficiency when heterozygousT P Dalton
Center for Environmental Genetics and the, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267 0056, USA
Biochem Biophys Res Commun 279:324-9. 2000..GCL is the rate-limiting step and represents a heterodimeric enzyme comprised of a catalytic subunit (GCLC) and a ("regulatory"), or modifier, subunit (GCLM)...
- Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinomaTalya L Dayton
David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Genes Dev 30:1020-33. 2016..Therefore, in addition to its role in cancer metabolism, PKM2 plays a role in controlling systemic metabolic homeostasis and inflammation, thereby preventing HCC by a non-cell-autonomous mechanism...
- Hepatocyte-specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failureYing Chen
Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH 45267 0056, and Center for Immunology and Inflammatory Disease, Massachusetts General Hospital, Boston, USA
Hepatology 45:1118-28. 2007..To explore the specific role of hepatic GSH in vivo, we targeted Gclc, a gene essential for GSH synthesis, so that it was flanked by loxP sites and used the albumin-cyclization ..
- Acoustic overstimulation facilitates the expression of glutamate-cysteine ligase catalytic subunit probably through enhanced DNA binding of activator protein-1 and/or NF-kappaB in the murine cochleaReiko Nagashima
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45 1 Nagaotoge cho, Hirakata, Osaka 573 0101, Japan
Neurochem Int 51:209-15. 2007..These results suggest that intense noise exposure facilitates the expression of GCL catalytic subunit in the cochlea possibly through the activation of transcription factors including AP-1 and NF-kappaB...
- A Glutathione-Nrf2-Thioredoxin Cross-Talk Ensures Keratinocyte Survival and Efficient Wound RepairMichèle Telorack
Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland
PLoS Genet 12:e1005800. 2016..Therefore, our study highlights a remarkable antioxidant capacity of the epidermis that ensures skin integrity and efficient wound healing. ..
- Perineuronal nets protect fast-spiking interneurons against oxidative stressJan Harry Cabungcal
Department of Psychiatry, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1008 Prilly Lausanne, Switzerland
Proc Natl Acad Sci U S A 110:9130-5. 2013..Abnormal perineuronal nets, as observed in the postmortem patient brain, may thus underlie the vulnerability and functional impairment of pivotal inhibitory circuits in schizophrenia...
- The LEGSKO mouse: a mouse model of age-related nuclear cataract based on genetic suppression of lens glutathione synthesisXingjun Fan
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
PLoS ONE 7:e50832. 2012..A floxed Gclc mouse was generated and crossed with a transgenic mouse expressing Cre in the lens to generate the LEGSKO mouse in ..
- Transforming growth factor β suppresses glutamate-cysteine ligase gene expression and induces oxidative stress in a lung fibrosis modelRui Ming Liu
Department of Environmental Health Sciences, School of Public Health, University of Alabama at Birmingham, AL 35294, USA
Free Radic Biol Med 53:554-63. 2012..Together, the data suggest that increased TGF-β1 expression may contribute to the GSH depletion observed in pulmonary fibrosis diseases and that GSH depletion may be an early event in, rather than a consequence of, fibrosis development...
- High expression of GCLC is associated with malignant melanoma of low oxidative phenotype and predicts a better prognosisDimitrios Mougiakakos
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
J Mol Med (Berl) 90:935-44. 2012..Here, we investigated the significance of the glutamate-L: -cysteine ligase catalytic subunit (GCLC) expression, a key regulator of glutathione synthesis, for malignant melanoma...
- Amniotic fluid activates the nrf2/keap1 pathway to repair an epidermal barrier defect in uteroAaron J Huebner
Department of Dermatology and Charles C Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado, Denver, CO 80045, USA
Dev Cell 23:1238-46. 2012..Our findings reveal that the functions of Nrf2 and the composition of amniotic fluid have coevolved to ensure the formation of a functional barrier...
- Neurotoxicity of domoic Acid in cerebellar granule neurons in a genetic model of glutathione deficiencyG Giordano
Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA 98105, USA
Mol Pharmacol 70:2116-26. 2006....
- Antioxidant activity in the newborn brain: a luciferase mouse modelGaute Dohlen
Department of Pediatric Research, Rikshospitalet Medical Center, Oslo, Norway
Neonatology 93:125-31. 2008..The aim of this study is to present a model that can monitor genetic activity in vivo during pregnancy and the first 10 days of life...
- Inducible alterations of glutathione levels in adult dopaminergic midbrain neurons result in nigrostriatal degenerationShankar J Chinta
Buck Institute for Age Research, Novato, California 94945, USA
J Neurosci 27:13997-4006. 2007..This suggests that depletion in glutathione within dopaminergic SN neurons has a direct impact on mitochondrial complex I activity via increased nitric oxide-related thiol oxidation and age-related dopaminergic SN cell loss...
- Homocysteine stimulates antioxidant response element-mediated expression of glutamate-cysteine ligase in mouse macrophagesFlorian Bea
Department of Internal Medicine III, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
Atherosclerosis 203:105-11. 2009..Real-time RT-PCR revealed increased mRNA-expression of the catalytic subunit of Gcl (Gclc) after treatment with homocysteine, and this occurred via increased transcription as demonstrated with luciferase ..
- Manipulation of cellular GSH biosynthetic capacity via TAT-mediated protein transduction of wild-type or a dominant-negative mutant of glutamate cysteine ligase alters cell sensitivity to oxidant-induced cytotoxicityDonald S Backos
Department of Pharmaceutical Sciences, Graduate Program in Toxicology, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA
Toxicol Appl Pharmacol 243:35-45. 2010..GCL) is the rate-limiting enzyme in GSH biosynthesis and is a heterodimeric holoenzyme composed of catalytic (GCLC) and modifier (GCLM) subunits...
- Silencing glycogen synthase kinase-3beta inhibits acetaminophen hepatotoxicity and attenuates JNK activation and loss of glutamate cysteine ligase and myeloid cell leukemia sequence 1Mie Shinohara
University of Southern California Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California 90089 9121, USA
J Biol Chem 285:8244-55. 2010..Taken together our results suggest that activation of GSK-3beta is a key mediator of the initial phase of APAP-induced liver injury through modulating GCL and Mcl-1 degradation, as well as JNK activation in liver...
- Hypoxia and kinase activity regulate lung epithelial cell glutathioneRobert M Jackson
Research Service, Miami VAHCS, Miami, Florida 33125, USA
Exp Lung Res 36:45-56. 2010..Liver GSH content (expressed per mg protein) was 20% less in MK2(-/-) mice than in nontransgenic Black 6 controls. Down-regulation of lung GSH content in hypoxia depends on peroxide tone of the cell and the p38(MAPK) system...
- Jun and JunD-dependent functions in cell proliferation and stress responseA Meixner
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria
Cell Death Differ 17:1409-19. 2010....
- Rapid activation of glutamate cysteine ligase following oxidative stressCecile M Krejsa
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 285:16116-24. 2010..The GCL holoenzyme consists of two separately coded proteins, a catalytic subunit (GCLC) and a modifier subunit (GCLM)...
- Delayed cardiomyopathy in dystrophin deficient mdx mice relies on intrinsic glutathione resourceLara Khouzami
Institut National de la Sante et de la Recherche Medicale, Institut Mondor de Recherche Biomedicale, Creteil, France
Am J Pathol 177:1356-64. 2010..In conclusion, low glutathione resource hastens the onset of cardiomyopathy linked to a defect in dystrophin in mdx mice. This is relevant to the glutathione deficiency that DMD patients may suffer...
- Attenuation of glomerular injury in diabetic mice with tert-butylhydroquinone through nuclear factor erythroid 2-related factor 2-dependent antioxidant gene activationHang Li
Departments of Histology and Embryology, Hebei Medical University, Shijiazhuang, PR China
Am J Nephrol 33:289-97. 2011..This study is aimed at examining the effect of tert-butylhydroquinone (tBHQ), an activator of Nrf2, on hyperglycemia-related diabetic nephropathy...
- Nox4 regulates Nrf2 and glutathione redox in cardiomyocytes in vivoAlison C Brewer
King s College London British Heart Foundation Centre of Research Excellence, Cardiovascular Division, London, UK
Free Radic Biol Med 51:205-15. 2011..These data therefore demonstrate that Nox4 can activate the Nrf2-regulated pathway, and suggest a potential role for Nox4 in the regulation of GSH redox in cardiomyocytes...
- Enzymatic defects underlying hereditary glutamate cysteine ligase deficiency are mitigated by association of the catalytic and regulatory subunitsMelanie Neely Willis
Department of Biochemistry and Redox Biology Center, University of Nebraska, Lincoln, Nebraska 68588 0664, USA
Biochemistry 50:6508-17. 2011..Human glutamate cysteine ligase is a heterodimer comprised of a catalytic subunit (GCLC) and a regulatory subunit (GCLM), which catalyzes the initial rate-limiting step in glutathione production...
- The mouse orthologue of the human ionotropic glutamate receptor-like gene (GRINL1A) maps(1) to mouse chromosome 9K S Wydner
Department of Biology, Saint Peter s College, Jersey City, NJ 07306, USA
Cytogenet Cell Genet 95:240-1. 2001
- Mapping of the glutamate-cysteine ligase catalytic subunit gene (GLCLC) to human chromosome 6p12 and mouse chromosome 9D-E and of the regulatory subunit gene (GLCLR) to human chromosome 1p21-p22 and mouse chromosome 3H1-3K Tsuchiya
Department of Pathology, University of Washington, Seattle, USA
Genomics 30:630-2. 1995
- Cloning/brain localization of mouse glutamylcysteine synthetase heavy chain mRNAY Kang
Division of Neurogerontology, Andrus Gerontology Center, University of Southern California, Los Angeles 90089 0191, USA
Neuroreport 8:2053-60. 1997..Variations in GCS levels and subsequent GSH synthesis may explain differences in susceptibility to neuropathology associated with oxidative stress noted in these various brain regions...
- Molecular cloning and sequencing of the cDNA encoding the catalytic subunit of mouse glutamate-cysteine ligaseL L Reid
Department of Environmental Health, University of Washington, Seattle, USA
Biochim Biophys Acta 1352:233-7. 1997..sequences encompassing the open reading frame for the catalytic subunit of mouse kidney glutamate-cysteine ligase (Glclc)...
- Expression of genes encoding antioxidant enzymes in human and mouse oocytes during the final stages of maturationS el Mouatassim
Laboratoire Marcel Merieux, cytogenetique, Avenue Tony Garnier BP 7322, 69357 Lyon, France
Mol Hum Reprod 5:720-5. 1999..This suggests the presence of maturation-specific polyadenylation of these transcripts. These enzymes can be considered as markers of cytoplasmic maturation...
- Glutathione synthesis is essential for mouse development but not for cell growth in cultureZ Z Shi
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
Proc Natl Acad Sci U S A 97:5101-6. 2000..These data demonstrate that GSH is required for mammalian development but dispensable in cell culture and that the functions of GSH, not GSH itself, are essential for cell growth...
- Modulation of glutathione and glutamate-L-cysteine ligase by methylmercury during mouse developmentS A Thompson
Department of Environmental Health, University of Washington, Seattle, Washington 98195, USA
Toxicol Sci 57:141-6. 2000..Western and Northern blots for Glcl-catalytic (Glclc) and Glcl-regulatory (Glclr) subunits were performed on gd 12 and gd 16 fetuses...
- Regulation of gamma-glutamate-cysteine ligase expression by oxidative stress in the mouse preimplantation embryoS K Stover
Department of Biological Sciences, University of Northern Colorado, Greeley, Colorado, 80639, USA
Toxicol Appl Pharmacol 168:153-9. 2000..These results suggest that, while the preimplantation embryo is well adapted to dealing with oxidative stress, it may be poorly protected from GSH-depleting toxicants...
- Expression of glutamate-cysteine ligase during mouse developmentDolores Diaz
Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA
Mol Reprod Dev 62:83-91. 2002..This enzyme is composed of two subunits: a large catalytic subunit (GCLc) and a smaller modifying subunit (GCLm), originating from different genes...
- Glutathione protects cells against arsenite-induced toxicityGeetha M Habib
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Free Radic Biol Med 42:191-201. 2007..Further, protection from arsenite-induced ubiquitination is mediated by GSH and to a lesser extent by available reducing equivalents in the cells...
- The role of H2O2 in the platelet-derived growth factor-induced transcription of the gamma-glutamylcysteine synthetase heavy subunitS Catarzi
Department of Biochemical Sciences, University of Firenze, Italy
Cell Mol Life Sci 59:1388-94. 2002..However, for the first time, in S1P-stimulated NIH 3T3 cells, increased levels of GCS-HS mRNA were shown to be related to increases in the reduced glutathione synthesis rate similar to those obtained after PMA and PDGF stimulation...
- Initial characterization of the glutamate-cysteine ligase modifier subunit Gclm(-/-) knockout mouse. Novel model system for a severely compromised oxidative stress responseYi Yang
Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH 45267 0056, USA
J Biol Chem 277:49446-52. 2002..In higher eukaryotes, this enzyme is a heterodimer comprising a catalytic subunit (GCLC) and a modifier subunit (GCLM), which change the catalytic characteristics of the holoenzyme...
- Glutamate-cysteine ligase attenuates TNF-induced mitochondrial injury and apoptosisDianne Botta
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA
Free Radic Biol Med 37:632-42. 2004..The rate-limiting enzyme in GSH synthesis is glutamate-cysteine ligase (GCL), which is composed of catalytic (GCLC) and modifier (GCLM) subunits...
- Effect of methylmercury on glutamate-cysteine ligase expression in the placenta and yolk sac during mouse developmentDolores Diaz
Department of Environmental Health, University of Washington, Mail Box 354695, 4225 Roosevelt Way NE, Seattle, WA 98195, USA
Reprod Toxicol 19:117-29. 2004..We also found that methylmercury induced GCLc mRNA expression in the placenta at gd 18 in a dose-dependent manner, suggesting an important role for this enzyme ..
- Smad3-ATF3 signaling mediates TGF-beta suppression of genes encoding Phase II detoxifying proteinsAndrei V Bakin
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
Free Radic Biol Med 38:375-87. 2005..b>GCLC, the gene that encodes the catalytic subunit of the enzyme glutamate cysteine ligase, the rate-limiting enzyme in ..
- Glutamate cysteine ligase catalysis: dependence on ATP and modifier subunit for regulation of tissue glutathione levelsYing Chen
Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 0056, USA
J Biol Chem 280:33766-74. 2005..gamma-GC may be produced by the catalytic subunit GCLC or by the holoenzyme (GCLholo), which comprises GCLC and the modifier subunit GCLM...
- Regulation of heavy subunit chain of gamma-glutamylcysteine synthetase by tumor necrosis factor-alpha in lens epithelial cells: role of LEDGF/p75Yoshihiro Takamura
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198 5840, USA
Am J Physiol Cell Physiol 290:C554-66. 2006....
- Acetaminophen-induced liver injury is attenuated in male glutamate-cysteine ligase transgenic miceDianne Botta
Department of Environmental and Occupational Health Sciences, Comparative Medicine, and Pathology, and UW NIEHS Center for Ecogenetics and Environmental Health, University of Washington, Seattle, Washington 68105, USA
J Biol Chem 281:28865-75. 2006..Because people are known to vary in their glutamate-cysteine ligase activity, this enzyme may also be an important determinant of sensitivity to acetaminophen-induced liver injury in humans...
- Expression of genes encoding antioxidant enzymes in preimplantation mouse and cow embryos and primary bovine oviduct cultures employed for embryo cocultureM B Harvey
Department of Medical Biochemistry, University of Calgary, AB, Canada
Biol Reprod 53:532-40. 1995..These experiments suggest that differences in gene expression may contribute to the variation in the ability of embryos to develop in vitro with respect to levels of oxygen and dependence on coculture...
- Embryonic lethality and liver degeneration in mice lacking the metal-responsive transcriptional activator MTF-1C Gunes
Institut fur Molekularbiologie, Abteilung II der Universität Zürich, Zurich, Switzerland
EMBO J 17:2846-54. 1998..We also note that the MTF-1 null mutant phenotype bears some similarity to those of two other regulators of cellular stress response, namely c-Jun and NF-kappaB (p65/RelA)...
- Assignment of a disintegrin and metalloproteinase domain 10 (Adam10) gene to mouse chromosome 9K Yamazaki
Tsukuba Research Laboratories, Eisai Co, Ltd, Ibaraki, Japan
Genomics 46:528-9. 1997
- Glutathione deficiency & immune dysfunction during agingRui Ming Liu; Fiscal Year: 2006....
- RESPONSE TO INJURY IN GAMMAGLUTAMYL CYCLE DEFICIENT MICEGEETHA HABIB; Fiscal Year: 2004..4. Only low levels of GSH are needed for development and survival of unstressed mice. These low levels of GSH render mice hypersensitive to chemical injury. ..
- FUNCTION OF GAMMA GLUTAMYL LEUKOTRIENASEGEETHA HABIB; Fiscal Year: 2005..4. Testing of the hypothesis that LTD4 is the principal cysteinyl LT mediator of bronchial asthma. ..
- Mechanisms of TGFbeta-mediated fibroblastic transitionAndrei Bakin; Fiscal Year: 2006..The proposed research will help to define the TGFbeta signaling network and will facilitate the design of novel selective inhibition of TGFbeta's tumor promoting activity. ..