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Gene Review

Mt3  -  metallothionein 3

Rattus norvegicus

Synonyms: GIF, Growth inhibitory factor, MT-3, MT-III, Metallothionein-3, ...
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Disease relevance of Mt3

  • Expression of growth inhibitory factor (metallothionein-III) mRNA and protein following excitotoxic immature brain injury [1].
  • Ischemia induces metallothionein III expression in neurons of rat brain [2].
  • In order to confirm the precise localization of MT-III in normal rat brain and the change of MT-III expression after transient whole brain ischemia, we raised a high affinity phagemid-antibody specific for rat MT-III [2].
  • The patterns of changes in relative expression levels of GIF and GFAP were quite similar to those in our previous studies on effects of cerebral stab wounds in rats, although the changes were more rapid in the previous studies [3].
  • The results indicated that GIF could play an important role in the repair after brain damage and also produce new insights into the mechanism of gliosis investigated mainly from the viewpoint of GFAP [4].

Psychiatry related information on Mt3


High impact information on Mt3


Chemical compound and disease context of Mt3

  • These results suggest that MT-III plays an important role in protecting neurons from ischemic insult by reducing neurotoxic zinc levels and inhibits uncontrolled growth of neurites after ischemia [2].
  • The most prominent findings in this study are, a very strong reaction of GIF and GIF mRNA in the reactive astrocytes around the site of injury induced by stab wound or kainic acid injection [9].

Biological context of Mt3


Anatomical context of Mt3


Associations of Mt3 with chemical compounds


Regulatory relationships of Mt3

  • Interestingly, most MT in control rat cerebrum and cerebellum was accounted for by MT-III, with MT-I/II being less than 10% [21].

Other interactions of Mt3


Analytical, diagnostic and therapeutic context of Mt3

  • Compared with the control group, the stress groups had higher inductions of MTs and MT-1 and MT-3 mRNA in hippocampus [24].
  • Because no information is available on this factor in relation to immature brain damage, we examined the chronological changes of GIF (MT-III) mRNA and protein following excitotoxic lesions to the postnatal day 9 brain using in situ hybridization and immunocytochemical techniques [1].
  • ELISA and Northern blot analysis revealed that MT-III protein as well as mRNA levels were up-regulated in cerebrum soon after ischemic stress [2].
  • In the caput, MT III mRNA levels decreased following orchidectomy, but control levels were maintained by testosterone [25].
  • To clarify the biological functions of GIF and GFAP in repair of the CNS, we examined changes in their relative levels to sham control using a Western blotting technique in the rat left hemisphere following occlusion of the left middle cerebral artery, for 28 days after surgery [3].


  1. Expression of growth inhibitory factor (metallothionein-III) mRNA and protein following excitotoxic immature brain injury. Acarin, L., Carrasco, J., González, B., Hidalgo, J., Castellano, B. J. Neuropathol. Exp. Neurol. (1999) [Pubmed]
  2. Ischemia induces metallothionein III expression in neurons of rat brain. Yanagitani, S., Miyazaki, H., Nakahashi, Y., Kuno, K., Ueno, Y., Matsushita, M., Naitoh, Y., Taketani, S., Inoue, K. Life Sci. (1999) [Pubmed]
  3. Patterns of growth inhibitory factor (GIF) and glial fibrillary acidic protein relative level changes differ following left middle cerebral artery occlusion in rats. Inuzuka, T., Hozumi, I., Tamura, A., Hiraiwa, M., Tsuji, S. Brain Res. (1996) [Pubmed]
  4. 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]
  5. 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]
  6. Role of hippocampal M1 and M4 muscarinic receptor subtypes in memory consolidation in the rat. Ferreira, A.R., Fürstenau, L., Blanco, C., Kornisiuk, E., Sánchez, G., Daroit, D., Castro e Silva, M., Cerveñansky, C., Jerusalinsky, D., Quillfeldt, J.A. Pharmacol. Biochem. Behav. (2003) [Pubmed]
  7. Peripheral melatonin mediates neural stimulation of duodenal mucosal bicarbonate secretion. Sjöblom, M., Jedstedt, G., Flemström, G. J. Clin. Invest. (2001) [Pubmed]
  8. The distribution of zinc selenite and expression of metallothionein-III mRNA in the spinal cord and dorsal root ganglia of the rat suggest a role for zinc in sensory transmission. Velázquez, R.A., Cai, Y., Shi, Q., Larson, A.A. J. Neurosci. (1999) [Pubmed]
  9. Expression of growth inhibitory factor (GIF) in normal and injured rat brains. Anezaki, T., Ishiguro, H., Hozumi, I., Inuzuka, T., Hiraiwa, M., Kobayashi, H., Yuguchi, T., Wanaka, A., Uda, Y., Miyatake, T. Neurochem. Int. (1995) [Pubmed]
  10. Structural and functional analysis of the rat metallothionein III genomic locus. Chapman, G.A., Kay, J., Kille, P. Biochim. Biophys. Acta (1999) [Pubmed]
  11. Differential display proteome analysis of PC-12 cells transiently transfected with metallothionein-3 gene. Zhou, B., Yang, W., Ji, J.G., Ru, B.G. J. Proteome Res. (2004) [Pubmed]
  12. The effects of melatonin on Ca(2+) homeostasis in endothelial cells. Pogan, L., Bissonnette, P., Parent, L., Sauvé, R. J. Pineal Res. (2002) [Pubmed]
  13. 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]
  14. Differential regulation of metallothionein-I, II, and III mRNA expression in the rat brain following kainic acid treatment. Kim, D., Kim, E.H., Kim, C., Sun, W., Kim, H.J., Uhm, C.S., Park, S.H., Kim, H. Neuroreport (2003) [Pubmed]
  15. 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]
  16. 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]
  17. Effects of clofibrate on flow cytometric populations in rat liver. Tomioka, Y., Suzuki, H., Miura, K., Yamaguchi, T., Hishinuma, T., Mizugaki, M. Methods and findings in experimental and clinical pharmacology. (1996) [Pubmed]
  18. Expression and functional characterization of the mt1 melatonin receptor from rat brain in Xenopus oocytes: evidence for coupling to the phosphoinositol pathway. Blumenau, C., Berger, E., Fauteck, J.D., Madeja, M., Wittkowski, W., Speckmann, E.J., Musshoff, U. J. Pineal Res. (2001) [Pubmed]
  19. Melatonin inhibits outward delayed rectifier potassium currents in hippocampal CA1 pyramidal neuron via intracellular indole-related domains. Hou, S.W., Zheng, P., Sun, F.Y. J. Pineal Res. (2004) [Pubmed]
  20. Temporalspatial patterns of expression of metallothionein-I and -III and other stress related genes in rat brain after kainic acid-induced seizures. Dalton, T., Pazdernik, T.L., Wagner, J., Samson, F., Andrews, G.K. Neurochem. Int. (1995) [Pubmed]
  21. Alterations of metallothionein isomers in Hg(0)-exposed rat brain. Yasutake, A., Nagano, M., Hirayama, K. Arch. Toxicol. (2003) [Pubmed]
  22. Growth inhibitory factor prevents degeneration of injured adult rat motoneurons. Sakamoto, T., Kawazoe, Y., Uchida, Y., Hozumi, I., Inuzuka, T., Watabe, K. Neuroreport (2003) [Pubmed]
  23. 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]
  24. 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]
  25. Expression and regulation of metallothioneins in the rat epididymis. Cyr, D.G., Dufresne, J., Pillet, S., Alfieri, T.J., Hermo, L. J. Androl. (2001) [Pubmed]
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