Disease relevance of MT3

• The gain in MT3 expression when cells were grown as heterotransplants was also shown to occur for the MCF-7, T-47D, Hs 578t, MDA-MB-231 breast cancer, and the PC-3 prostate cancer cell lines [1].
• In contrast, 103 of 107 (96.26%) high-grade urothelial cancers and 17 of 17 (100%) specimens of carcinoma in situ stained positive for the MT3 protein [1].
• An isomer of MTs, MT3, of particular interest, was originally discovered as a growth inhibitory factor, and has been found to be markedly reduced in the brain of patients with Alzheimer's disease and several other neurodegenerative diseases [2].
• The ability of accessory cells to present mumps antigen in the context of this supertypic restriction determinant was blocked by a monoclonal antibody specific for MT3 [3].
• In SCID mice, the concentrations of human immunoglobulin G, antithyroglobulin and antithyroperoxidase antibodies in sera were not significantly changed by injecting MT3 [4].
• MT3 seems to accumulate in the cytoplasm of adrenocortical carcinoma cells, in contrast to benign cells of aldosterone-producing adenomas, which present MT3 in the nuclei [5].

Psychiatry related information on MT3

• MT3, also known as Growth Inhibitory Factor (GIF), is postulated to inhibit neuron outgrowth in Alzheimer's disease [6].
• A quantitative Western blot analysis also revealed that MT-I/II protein accumulated in CJD brain with a short disease duration, whereas MT3 in CJD brain with a long disease duration was statistically significantly reduced in comparison to the normal brains [7].

High impact information on MT3

• MT3 not only switches T cells from the formation of IgE-PF to the formation of IgE-SF, it also facilitates the generation of antigen-specific suppressor T cells which produce antigen-specific GIF upon antigenic stimulation [8].
• Molecular localization of human class II MT2 and MT3 determinants [9].
• MT3 is abundant in the normal human brain, but greatly reduced in the Alzheimer's disease (AD) brain [10].
• In the AD cortex, the number of MT3-positive astrocytes is drastically reduced, suggesting that MT3 is down-regulated in this subset of glial cells during AD [10].
• GIF inhibited survival and neurite formation of cortical neurons in vitro [10].
• The MT3 protein is present in the zona glomerulosa of the human adrenal cortex, in significantly higher ammounts than in the other adrenocortical layers (ie. the zona fasciculata and zona reticularis) [5].
• Interestingly, the ammounts of cytoplasmic and nuclear MT3 vary in the non-pathological adrenal cortex and adrenals of patients with idiopathic hyperaldosteronism, with a higher proportion of nuclear/cytoplasmic concentrations of MT3 in the zona glomerulosa of the latter [5].
• In addition to the almost exclusive nuclear expression of MT3 in aldosterone-producing adenomas of the adrenal, and the regulation of MT3 mRNA levels by angiotensin-II in H295R cells, the findings above suggest a possible functional role of MT3 in adrenocortical aldosterone biosynthesis [5].

Chemical compound and disease context of MT3

• Treatment of the gastric cancer cell lines with 5-azacytidine resulted in new expression of MT3 mRNA in these cells [11].
• Zn(II) complexes of human and mouse MT3 inhibit the survival of rat cortical neurons cultured in the presence of an Alzheimer's disease brain extract [12].
• Additionally, the down-regulation of MT3 may be a main factor in the decrease of the scavenging ability for the free OH* and O2(*-) radicals, which is possibly associated with the pathogenesis of neurodegenerative disease [13].

Biological context of MT3

• MT3 shows apparently different properties and function from MT1 even though they have 70% sequence homology [14].
• The results showed that transient overexpression of human MT1A, MT2 and MT3 genes dynamically affected cell viability, and the effect was influenced by zinc and cadmium ions [15].
• However, the reaction of the E23K mutant with SNOC exhibited biphasic kinetics and the mutant protein released zinc ions much faster than MT3 in the initial step, while MT3 exhibited single kinetic process [16].
• MT3 fulfills unique biological roles in homeostasis of the central nervous system and in the etiology of neuropathological disorders [2].
• Protective effect of MT3 on DNA damage in response to reactive oxygen species [17].

Anatomical context of MT3

• Molecular identifications of HLA-DR4, MT3, and TB21 antigens on HLA-DR4 homozygous B cell lines [18].
• Furthermore, when comparisons were possible, the MT3 pharmacological characteristics were similar to those described in the literature for hamster brain and testis [19].
• Antigen-specific HLA-restricted human T-cell lines. I. An MT3-like restriction determinant distinct from HLA-DR [3].
• MT3 was added to cultured peripheral blood mononuclear cells (PBMC) from patients with AITD and was additionally injected into severe combined immunodeficient (SCID) mice to which Graves' thyroid cells and intrathyroidal lymphocytes were engrafted [4].
• Because MT3 is also expressed by the normal and ALS spinal cord, it is a central nervous system-specific and not only a brain-specific protein [20].

Associations of MT3 with chemical compounds

• A series of MT3 variants around the EAAEAE hexapeptide have been prepared by site-directed mutagenesis and their properties and reactivity towards pH, EDTA and DTNB have been studied [14].
• We suggest the hydroxyl group in human GIF may help stabilize the biologically active conformation [6].
• MT3 was also able to efficiently remove the superoxide anion, which was generated from the xanthine/xanthine oxidase system [17].
• In this study, we show that MT3 is able to protect against the DNA damage induced by ferric ion-nitrilotriacetic acid and H(2)O(2), and that this protective effect is inhibited by the alkylation of the sulfhydryl groups of MT-III by treatment with EDTA and N-ethylmaleimide [17].
• Results showed that apo-MT3 and apo-MT2 have almost equal helical content (approximately 10%) in aqueous buffer, but that MT- had slightly higher tendency to form alpha-helical secondary structure in TFE-water mixtures [21].

Physical interactions of MT3

• Results demonstrate that MT3 binds Zn2+ and Cd2+ ions more weakly than MT2 but expresses higher metal-binding capacity and plasticity [21].

Regulatory relationships of MT3

• Using an 8-oxoguanine DNA glycosylase (OGG1)-specific siRNAs, we also found that MT3 expression resulted in the suppression of the gamma-radiation-induced 8-oxoG accumulation and mutation in the OGG1-depleted cells [22].
• MT3 stimulated proliferation of PBMC when cultured for 2 to 3 days in patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) and in normal controls (NC) [4].

Analytical, diagnostic and therapeutic context of MT3

• A series of human MT3 mutants were constructed and their biochemical properties characterized by UV spectroscopy, circular dichroism spectroscopy, EDTA reaction, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) reaction, and pH titration [6].
• Using a cell culture model (UROtsa), it was demonstrated that expression of the MT3 protein was not required for malignant transformation of urothelial cells by either Cd(+2) or As(+3) [1].
• During the course of bioassay, we found out unexpectedly that mutation at E23 of hMT3 eliminates the neuronal growth inhibitory activity completely [16].
• Molecular characterization of MT3 antigens by two-dimensional gel electrophoresis, NH2-terminal amino acid sequence analysis, and southern blot analysis [23].
• Southern blot analysis of genomic DNA from HLA-DR1 through -DR7 homozygous cell lines with DR beta-chain gene probes reveals a striking similarity in the pattern of hybridizing fragments between DR4 and DR7 haplotypes and among DR3, DR5, and DRw6 haplotypes reminiscent of the MT3/MT2 allodeterminant distribution [23].

References