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Gene Review

Gclm  -  glutamate-cysteine ligase, modifier subunit

Mus musculus

Synonyms: AI649393, GCS light chain, Gamma-ECS regulatory subunit, Gamma-glutamylcysteine synthetase regulatory subunit, Gcmc, ...
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Disease relevance of Gclm


Psychiatry related information on Gclm

  • This study investigated the role of cellular antioxidant defense mechanisms in modulating the neurotoxicity of domoic acid (DomA), by using cerebellar granule neurons (CGNs) from mice lacking the modifier subunit of glutamate-cysteine ligase (Gclm) [4].

High impact information on Gclm


Chemical compound and disease context of Gclm

  • To further characterize the role of glutathione and oxidative stress in the toxicity of arsenic, we have used fetal fibroblasts from Gclm(-/-) mice, which lack the modifier subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis [10].
  • We Studied the effect of GSH depletion by buthionine sulfoximine (BSO), a potent inhibitor of gamma-glutamylcysteine synthetase, on doxorubicin (DOX) toxicity in mice [11].

Biological context of Gclm


Anatomical context of Gclm


Associations of Gclm with chemical compounds


Regulatory relationships of Gclm


Other interactions of Gclm


Analytical, diagnostic and therapeutic context of Gclm


  1. Initial characterization of the glutamate-cysteine ligase modifier subunit Gclm(-/-) knockout mouse. Novel model system for a severely compromised oxidative stress response. Yang, Y., Dieter, M.Z., Chen, Y., Shertzer, H.G., Nebert, D.W., Dalton, T.P. J. Biol. Chem. (2002) [Pubmed]
  2. The gamma-glutamylcysteine synthetase and glutathione regulate asbestos-induced expression of activator protein-1 family members and activity. Shukla, A., Flanders, T., Lounsbury, K.M., Mossman, B.T. Cancer Res. (2004) [Pubmed]
  3. Influence of buthionine sulfoximine and misonidazole on glutathione level and radiosensitivity of human tumor xenografts. Guichard, M., Lespinasse, F., Malaise, E.P. Radiat. Res. (1986) [Pubmed]
  4. Neurotoxicity of domoic Acid in cerebellar granule neurons in a genetic model of glutathione deficiency. Giordano, G., White, C.C., McConnachie, L.A., Fernandez, C., Kavanagh, T.J., Costa, L.G. Mol. Pharmacol. (2006) [Pubmed]
  5. Mitochondrial damage in muscle occurs after marked depletion of glutathione and is prevented by giving glutathione monoester. Mårtensson, J., Meister, A. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  6. Intracellular cysteine delivery system that protects against toxicity by promoting glutathione synthesis. Williamson, J.M., Boettcher, B., Meister, A. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  7. Evidence that the gamma-glutamyl cycle functions in vivo using intracellular glutathione: effects of amino acids and selective inhibition of enzymes. Griffith, O.W., Bridges, R.J., Meister, A. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  8. Vanin-1-/- mice exhibit a glutathione-mediated tissue resistance to oxidative stress. Berruyer, C., Martin, F.M., Castellano, R., Macone, A., Malergue, F., Garrido-Urbani, S., Millet, V., Imbert, J., Duprè, S., Pitari, G., Naquet, P., Galland, F. Mol. Cell. Biol. (2004) [Pubmed]
  9. A novel missense mutation in the gamma-glutamylcysteine synthetase catalytic subunit gene causes both decreased enzymatic activity and glutathione production. Hamilton, D., Wu, J.H., Alaoui-Jamali, M., Batist, G. Blood (2003) [Pubmed]
  10. Butylhydroquinone protects cells genetically deficient in glutathione biosynthesis from arsenite-induced apoptosis without significantly changing their prooxidant status. Kann, S., Estes, C., Reichard, J.F., Huang, M.Y., Sartor, M.A., Schwemberger, S., Chen, Y., Dalton, T.P., Shertzer, H.G., Xia, Y., Puga, A. Toxicol. Sci. (2005) [Pubmed]
  11. Effect of glutathione depletion by buthionine sulfoximine on doxorubicin toxicity in mice. Kisara, S., Furusawa, S., Takayanagi, Y., Sasaki, K. Res. Commun. Mol. Pathol. Pharmacol. (1995) [Pubmed]
  12. 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]
  13. Glutamate-cysteine ligase modifier subunit: mouse Gclm gene structure and regulation by agents that cause oxidative stress. Solis, W.A., Dalton, T.P., Dieter, M.Z., Freshwater, S., Harrer, J.M., He, L., Shertzer, H.G., Nebert, D.W. Biochem. Pharmacol. (2002) [Pubmed]
  14. 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]
  15. 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]
  16. Long exposure to high glucose concentration impairs the responsive expression of gamma-glutamylcysteine synthetase by interleukin-1beta and tumor necrosis factor-alpha in mouse endothelial cells. Urata, Y., Yamamoto, H., Goto, S., Tsushima, H., Akazawa, S., Yamashita, S., Nagataki, S., Kondo, T. J. Biol. Chem. (1996) [Pubmed]
  17. Nepsilon-(Carboxymethyl)lysine induces gamma-glutamylcysteine synthetase in RAW264.7 cells. Miyahara, Y., Ikeda, S., Muroya, T., Yasuoka, C., Urata, Y., Horiuchi, S., Kohno, S., Kondo, T. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  18. Induction of glutamate-cysteine ligase (gamma-glutamylcysteine synthetase) in the brains of adult female mice subchronically exposed to methylmercury. Thompson, S.A., White, C.C., Krejsa, C.M., Diaz, D., Woods, J.S., Eaton, D.L., Kavanagh, T.J. Toxicol. Lett. (1999) [Pubmed]
  19. Differential inhibition of glutamine and gamma-glutamylcysteine synthetases by alpha-alkyl analogs of methionine sulfoximine that induce convulsions. Griffith, O.W., Meister, A. J. Biol. Chem. (1978) [Pubmed]
  20. A spectrophotometric assay of gamma-glutamylcysteine synthetase and glutathione synthetase in crude extracts from tissues and cultured mammalian cells. Volohonsky, G., Tuby, C.N., Porat, N., Wellman-Rousseau, M., Visvikis, A., Leroy, P., Rashi, S., Steinberg, P., Stark, A.A. Chem. Biol. Interact. (2002) [Pubmed]
  21. Molecular cloning and sequencing of the cDNA encoding mouse glutamate-cysteine ligase regulatory subunit. Reid, L.L., Botta, D., Shao, J., Hudson, F.N., Kavanagh, T.J. Biochim. Biophys. Acta (1997) [Pubmed]
  22. Cloning and characterization of the proximal promoter region of the mouse glutamate-L-cysteine ligase regulatory subunit gene. Hudson, F.N., Kavanagh, T.J. Biochim. Biophys. Acta (2000) [Pubmed]
  23. Buthionine sulfoximine-mediated depletion of glutathione in intracranial human glioma-derived xenografts. Skapek, S.X., Colvin, O.M., Griffith, O.W., Groothuis, D.R., Colapinto, E.V., Lee, Y., Hilton, J., Elion, G.B., Bigner, D.D., Friedman, H.S. Biochem. Pharmacol. (1988) [Pubmed]
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