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Gene Review

Gclc  -  glutamate-cysteine ligase, catalytic subunit

Mus musculus

Synonyms: D9Wsu168e, GCS heavy chain, GLCL-H, Gamma-ECS, Gamma-glutamylcysteine synthetase, ...
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Disease relevance of Gclc


High impact information on Gclc


Biological context of Gclc

  • In the current study, we investigated the tissue distribution of Gclc and Gclm transcripts, as well as GCLc protein, in the developing mouse embryo [8].
  • As an initial first step toward understanding the role of GSH in cellular redox homeostasis, we have targeted a disruption of the mouse Gclc gene [9].
  • Therefore, the Gclc(+/-) mouse may be a useful genetic model for mild endogenous oxidative stress [9].
  • The nonhomologous Gclc and Gclm genes are located on mouse chromosomes 9 and 3, respectively [9].
  • The Gclc(-/-) homozygous knockout animal dies before gestational day 13, whereas the Gclc(+/-) heterozygote is viable and fertile [9].

Anatomical context of Gclc


Associations of Gclc with chemical compounds


Regulatory relationships of Gclc

  • Thus, the yolk sac is capable of up-regulating Glclc and GSH synthetic capacity in response to MeHg exposure [11].

Other interactions of Gclc


Analytical, diagnostic and therapeutic context of Gclc


  1. Glutathione S-transferases--biomarkers of cancer risk and chemopreventive response. Clapper, M.L., Szarka, C.E. Chem. Biol. Interact. (1998) [Pubmed]
  2. Modulation of nonprotein sulphydryl compounds rhythm with buthionine sulphoximine: relationship with oxaliplatin toxicity in mice. Li, X.M., Metzger, G., Filipski, E., Lemaigre, G., Lévi, F. Arch. Toxicol. (1998) [Pubmed]
  3. Vanin-1(-/-) mice show decreased NSAID- and Schistosoma-induced intestinal inflammation associated with higher glutathione stores. Martin, F., Penet, M.F., Malergue, F., Lepidi, H., Dessein, A., Galland, F., de Reggi, M., Naquet, P., Gharib, B. J. Clin. Invest. (2004) [Pubmed]
  4. Embryonic lethality and liver degeneration in mice lacking the metal-responsive transcriptional activator MTF-1. Günes, C., Heuchel, R., Georgiev, O., Müller, K.H., Lichtlen, P., Blüthmann, H., Marino, S., Aguzzi, A., Schaffner, W. EMBO J. (1998) [Pubmed]
  5. Glutathione synthesis is essential for mouse development but not for cell growth in culture. Shi, Z.Z., Osei-Frimpong, J., Kala, G., Kala, S.V., Barrios, R.J., Habib, G.M., Lukin, D.J., Danney, C.M., Matzuk, M.M., Lieberman, M.W. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  6. Altered gene expression in the liver of gamma-glutamyl transpeptidase-deficient mice. Habib, G.M., Shi, Z.Z., Ou, C.N., Kala, G., Kala, S.V., Lieberman, M.W. Hepatology (2000) [Pubmed]
  7. Hepatocellular response to chemical stress in CD-1 mice: induction of early genes and gamma-glutamylcysteine synthetase. Kitteringham, N.R., Powell, H., Clement, Y.N., Dodd, C.C., Tettey, J.N., Pirmohamed, M., Smith, D.A., McLellan, L.I., Kevin Park, B. Hepatology (2000) [Pubmed]
  8. Expression of glutamate-cysteine ligase during mouse development. Díaz, D., Krejsa, C.M., Kavanagh, T.J. Mol. Reprod. Dev. (2002) [Pubmed]
  9. Knockout of the mouse glutamate cysteine ligase catalytic subunit (Gclc) gene: embryonic lethal when homozygous, and proposed model for moderate glutathione deficiency when heterozygous. Dalton, T.P., Dieter, M.Z., Yang, Y., Shertzer, H.G., Nebert, D.W. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  10. Induction of glutathione synthesis in macrophages by oxidized low-density lipoproteins is mediated by consensus antioxidant response elements. Bea, F., Hudson, F.N., Chait, A., Kavanagh, T.J., Rosenfeld, M.E. Circ. Res. (2003) [Pubmed]
  11. Modulation of glutathione and glutamate-L-cysteine ligase by methylmercury during mouse development. Thompson, S.A., White, C.C., Krejsa, C.M., Eaton, D.L., Kavanagh, T.J. Toxicol. Sci. (2000) [Pubmed]
  12. The role of H2O2 in the platelet-derived growth factor-induced transcription of the gamma-glutamylcysteine synthetase heavy subunit. Catarzi, S., Degl'Innocenti, D., Iantomasi, T., Favilli, F., Vincenzini, M.T. Cell. Mol. Life Sci. (2002) [Pubmed]
  13. Regulation of gamma-glutamate-cysteine ligase expression by oxidative stress in the mouse preimplantation embryo. Stover, S.K., Gushansky, G.A., Salmen, J.J., Gardiner, C.S. Toxicol. Appl. Pharmacol. (2000) [Pubmed]
  14. Different effects of nine clausenamide ennatiomers on liver glutathione biosynthesis and glutathione S-transferase activity in mice. Wu, Y.Q., Liu, L.D., Wei, H.L., Liu, G.T. Acta Pharmacol. Sin. (2006) [Pubmed]
  15. Glutathione, a first line of defense against cadmium toxicity. Singhal, R.K., Anderson, M.E., Meister, A. FASEB J. (1987) [Pubmed]
  16. Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion. Mérad-Saïdoune, M., Boitier, E., Nicole, A., Marsac, C., Martinou, J.C., Sola, B., Sinet, P.M., Ceballos-Picot, I. Exp. Neurol. (1999) [Pubmed]
  17. The generation of oxygen radicals: a positive signal for lymphocyte activation. Fidelus, R.K. Cell. Immunol. (1988) [Pubmed]
  18. Low-dose gamma-ray irradiation reduces oxidative damage induced by CCl4 in mouse liver. Nomura, T., Yamaoka, K. Free Radic. Biol. Med. (1999) [Pubmed]
  19. Effect of schisandrin B on hepatic glutathione antioxidant system in mice: protection against carbon tetrachloride toxicity. Ip, S.P., Poon, M.K., Wu, S.S., Che, C.T., Ng, K.H., Kong, Y.C., Ko, K.M. Planta Med. (1995) [Pubmed]
  20. Depletion of colonic detoxication enzyme activity in mice with dextran sulphate sodium-induced colitis. Clapper, M.L., Adrian, R.H., Pfeiffer, G.R., Kido, K., Everley, L., Cooper, H.S., Murthy, S. Aliment. Pharmacol. Ther. (1999) [Pubmed]
  21. Chronic glutathione depletion alters expression of enteric inhibitory neurochemicals in the mouse. Koch, T.R., Fink, J.G., Ruan, E., Petro, A., Opara, E.C. Neurosci. Lett. (1997) [Pubmed]
  22. Molecular cloning and sequencing of the cDNA encoding the catalytic subunit of mouse glutamate-cysteine ligase. Reid, L.L., Botta, D., Lu, Y., Gallagher, E.P., Kavanagh, T.J. Biochim. Biophys. Acta (1997) [Pubmed]
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