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Gene Review

Mt1a  -  metallothionein 1a

Rattus norvegicus

Synonyms: MT-1, MT-I, Metallothionein-1, Metallothionein-I, Mt, ...
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Disease relevance of Mt1a

  • These findings suggest that disruption of the SCKKSCC motif can inhibit proximal tubular MT uptake and thereby eliminate much of the renal accumulation and toxicity of heavy metals such as cadmium, gold, copper, and cisplatinum [1].
  • MT and Mn-SOD induced by cytokines in the liver exert an antioxidative role during acute phase response, therefore preventing tissues from injury by oxidative stress [2].
  • The refined metallothionein structure has a root-mean-square deviation of 0.016 A from ideality of bonds and normal stereochemistry of phi, phi and chi torsion angles [3].
  • Zinc or copper deficiency-induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes [4].
  • Protective role of metallothionein in stress-induced gastric ulcer in rats [5].

Psychiatry related information on Mt1a

  • The growth inhibitory factor (GIF) is a new metallothionein (MT)-like protein that is downregulated in Alzheimer's disease (AD) brain [6].
  • The results from a second experiment demonstrate that the attenuation of the MTII-induced anorexia was due to learned schedules of food intake rather than food deprivation per se [7].
  • In the present experiment, the effects of food and water deprivation alone or of immobilization stress plus food and water deprivation on liver, brain, and heart MT have been studied in adult male rats [8].
  • Our results indicate that MT-II has a very limited brain penetration capability, and its effect on feeding behavior following systemic administration may be mediated by either the brain regions in close proximity to the CVOs or sites outside of the BBB, including CVOs or other peripheral systems [9].
  • Unlike satiation, rats that received exposure after MTII exhibited continued high levels of responding to the tone [10].

High impact information on Mt1a


Chemical compound and disease context of Mt1a


Biological context of Mt1a


Anatomical context of Mt1a


Associations of Mt1a with chemical compounds


Physical interactions of Mt1a


Regulatory relationships of Mt1a


Other interactions of Mt1a

  • Third, megalin and fluorescently labeled MT colocalize in BN-16 cells, as shown by fluorescent microscopic techniques [1].
  • When recombinant MTs were added to cultures grown in the presence of brain extract, MT-III but not MT-I had an inhibitory effect on neuron survival, confirming that MT-III is a specific inhibitory factor in this assay [31].
  • Synergistic induction of metallothionein synthesis by interleukin-6, dexamethasone and zinc in the rat [32].
  • Endothelin-1-mediated alteration of metallothionein and trace metals in the liver and kidneys of chronically diabetic rats [24].
  • IL-11 and to a lesser extent LIF, are also potential mediators of MT synthesis in inflammation [33].

Analytical, diagnostic and therapeutic context of Mt1a


  1. Megalin mediates renal uptake of heavy metal metallothionein complexes. Klassen, R.B., Crenshaw, K., Kozyraki, R., Verroust, P.J., Tio, L., Atrian, S., Allen, P.L., Hammond, T.G. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  2. Antioxidative roles of metallothionein and manganese superoxide dismutase induced by tumor necrosis factor-alpha and interleukin-6. Sato, M., Sasaki, M., Hojo, H. Arch. Biochem. Biophys. (1995) [Pubmed]
  3. Refined crystal structure of Cd, Zn metallothionein at 2.0 A resolution. Robbins, A.H., McRee, D.E., Williamson, M., Collett, S.A., Xuong, N.H., Furey, W.F., Wang, B.C., Stout, C.D. J. Mol. Biol. (1991) [Pubmed]
  4. Zinc or copper deficiency-induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes. Penkowa, M., Giralt, M., Thomsen, P.S., Carrasco, J., Hidalgo, J. J. Neurotrauma (2001) [Pubmed]
  5. Protective role of metallothionein in stress-induced gastric ulcer in rats. Jiang, P., Chang, L., Pan, C.S., Qi, Y.F., Tang, C.S. World J. Gastroenterol. (2005) [Pubmed]
  6. Changes of growth inhibitory factor after stab wounds in rat brain. Hozumi, I., Inuzuka, T., Hiraiwa, M., Uchida, Y., Anezaki, T., Ishiguro, H., Kobayashi, H., Uda, Y., Miyatake, T., Tsuji, S. Brain Res. (1995) [Pubmed]
  7. Learned meal initiation attenuates the anorexic effects of the melanocortin agonist MTII. Benoit, S.C., Clegg, D.J., Barrera, J.G., Seeley, R.J., Woods, S.C. Diabetes (2003) [Pubmed]
  8. Liver, brain, and heart metallothionein induction by stress. Hidalgo, J., Borrás, M., Garvey, J.S., Armario, A. J. Neurochem. (1990) [Pubmed]
  9. Exploring the site of anorectic action of peripherally administered synthetic melanocortin peptide MT-II in rats. Trivedi, P., Jiang, M., Tamvakopoulos, C.C., Shen, X., Yu, H., Mock, S., Fenyk-Melody, J., Van der Ploeg, L.H., Guan, X.M. Brain Res. (2003) [Pubmed]
  10. The role of the hypothalamic melanocortin system in behavioral appetitive processes. Benoit, S.C., Tracy, A.L., Air, E.L., Kinzig, K., Seeley, R.J., Davidson, T.L. Pharmacol. Biochem. Behav. (2001) [Pubmed]
  11. Activation of a heterologous promoter in response to dexamethasone and cadmium by metallothionein gene 5'-flanking DNA. Karin, M., Haslinger, A., Holtgreve, H., Cathala, G., Slater, E., Baxter, J.D. Cell (1984) [Pubmed]
  12. Partial correction of murine hereditary growth disorder by germ-line incorporation of a new gene. Hammer, R.E., Palmiter, R.D., Brinster, R.L. Nature (1984) [Pubmed]
  13. Chelation of cadmium with BAL and DTPA in rats. Cherian, M.G. Nature (1980) [Pubmed]
  14. Detection of circulating metallothionein in rats injected with zinc or cadmium. Garvey, J.S., Chang, C.C. Science (1981) [Pubmed]
  15. Alternative inducers of the rat metallothionein I gene cause distinct changes in chromatin structure in the 5' region of the gene. Taplitz, S.J., Calame, K.L., Herschman, H.R. Mol. Cell. Biol. (1986) [Pubmed]
  16. Suppression of metallothionein gene expression in a rat hepatoma because of promoter-specific DNA methylation. Ghoshal, K., Majumder, S., Li, Z., Dong, X., Jacob, S.T. J. Biol. Chem. (2000) [Pubmed]
  17. Antiapoptotic effect and inhibition of ischemia/reperfusion-induced myocardial injury in metallothionein-overexpressing transgenic mice. Kang, Y.J., Li, Y., Sun, X., Sun, X. Am. J. Pathol. (2003) [Pubmed]
  18. Metallothionein isoforms (I+II and III) and interleukin-6 in the hippocampus of old rats: may their concomitant increments lead to neurodegeneration? Mocchegiani, E., Giacconi, R., Fattoretti, P., Casoli, T., Cipriano, C., Muti, E., Malavolta, M., DiStefano, G., Bertoni-Freddari, C. Brain Res. Bull. (2004) [Pubmed]
  19. Interleukin 6 regulates metallothionein gene expression and zinc metabolism in hepatocyte monolayer cultures. Schroeder, J.J., Cousins, R.J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  20. Endotoxin and intracerebroventricular injection of IL-1 and IL-6 induce rat brain metallothionein-I and -II. Hernández, J., Hidalgo, J. Neurochem. Int. (1998) [Pubmed]
  21. Interleukin-6 and tumor necrosis factor-alpha type 1 receptor deficient mice reveal a role of IL-6 and TNF-alpha on brain metallothionein-I and -III regulation. Carrasco, J., Hernandez, J., Bluethmann, H., Hidalgo, J. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  22. Effect of zinc, copper and glucocorticoids on metallothionein levels of cultured neurons and astrocytes from rat brain. Hidalgo, J., García, A., Oliva, A.M., Giralt, M., Gasull, T., González, B., Milnerowicz, H., Wood, A., Bremner, I. Chem. Biol. Interact. (1994) [Pubmed]
  23. Efficacy of zinc treatment against iron-induced toxicity in rat hepatoma cell line H4-II-E-C3. Formigari, A., Santon, A., Irato, P. Liver Int. (2007) [Pubmed]
  24. Endothelin-1-mediated alteration of metallothionein and trace metals in the liver and kidneys of chronically diabetic rats. Cai, L., Chen, S., Evans, T., Cherian, M.G., Chakrabarti, S. Int. J. Exp. Diabetes Res. (2002) [Pubmed]
  25. Growth inhibitory factor prevents neurite extension and the death of cortical neurons caused by high oxygen exposure through hydroxyl radical scavenging. Uchida, Y., Gomi, F., Masumizu, T., Miura, Y. J. Biol. Chem. (2002) [Pubmed]
  26. Metallothionein-like cadmium binding protein in rat testes administered with cadmium and selenium. Ohta, H., Seki, Y., Imamiya, S. Bulletin of environmental contamination and toxicology. (1988) [Pubmed]
  27. Alterations of metallothionein isomers in Hg(0)-exposed rat brain. Yasutake, A., Nagano, M., Hirayama, K. Arch. Toxicol. (2003) [Pubmed]
  28. Cell fractionation in non-ionic detergent distinguishes sub-populations of polyoma virus middle T antigen and reveals a novel form. Krauzewicz, N., Elliott, J., Griffin, B.E. Oncogene (1994) [Pubmed]
  29. Stable expression of a functional GluR6 homomeric glutamate receptor channel in mammalian cells. Tygesen, C.K., Rasmussen, J.S., Jones, S.V., Hansen, A., Hansen, K., Andersen, P.H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  30. Hypermethylation of metallothionein-I promoter and suppression of its induction in cell lines overexpressing the large subunit of Ku protein. Majumder, S., Ghoshal, K., Li, Z., Jacob, S.T. J. Biol. Chem. (1999) [Pubmed]
  31. Enhanced neurotrophic activity in Alzheimer's disease cortex is not associated with down-regulation of metallothionein-III (GIF). Erickson, J.C., Sewell, A.K., Jensen, L.T., Winge, D.R., Palmiter, R.D. Brain Res. (1994) [Pubmed]
  32. Synergistic induction of metallothionein synthesis by interleukin-6, dexamethasone and zinc in the rat. Sato, M., Yamaki, J., Hamaya, M., Hojo, H. Int. J. Immunopharmacol. (1996) [Pubmed]
  33. Metallothionein induction in cultured rat hepatocytes by arthritic rat serum, activated macrophages, interleukin-6, interleukin-11 and leukaemia inhibitory factor. Coyle, P., Philcox, J.C., Rofe, A.M. Inflamm. Res. (1995) [Pubmed]
  34. Effects of zinc on the induction of metallothionein isoforms in hippocampus in stress rats. Chen, W.Q., Cheng, Y.Y., Zhao, X.L., Li, S.T., Hou, Y., Hong, Y. Exp. Biol. Med. (Maywood) (2006) [Pubmed]
  35. Localization of metallothionein (MT) and expression of MT isoforms induced by cadmium in rat dental pulp. Sogawa, C.A., Sogawa, N., Yamamoto, T., Oda, N., Inoue, T., Onodera, K., Furuta, H. Jpn. J. Pharmacol. (2001) [Pubmed]
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