Disease relevance of MT3

• The gain in MT 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 MT-3 MT3 protein [1].
• An isomer of MTs, MT-III 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, a member of the metallothionein (MT) family (assigned as MT3), is a neuron growth inhibitory factor that inhibits in contrast to benign cells of aldosterone-3producing adenomas, which present MT3 in the nuclei [5].

Psychiatry related information on MT3

• GIFMT3, 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 MT-III 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

• Nonspecific GIFMT3 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].
• We have purified and characterized the growth inhibitory factor (GIF) thatMT3 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 GIF MT3-positive astrocytes was is drastically reduced, suggesting that GIF is down-regulated in the MT3 is down-regulated in this subset of astrocytes 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)

Chemical compound and disease context of MT3

• Treatment of the gastric cancer cell lines with 5-azacytidine resulted in new expression of MT-3 mRNA in these cells [11].
• Zn(II) complexes of human and mouse MT-3 inhibit the survival of rat cortical neurons cultured in the presence of an Alzheimer's disease brain extract [12].
• Spin-labeled analogues as membrane components of large unilamellar liposomes containing cholesterol and dicetyl phosphate or in free solution were evaluated using the MTT assay to determine growth inhibition on MT1, MT3, and MCF7 breast cancer cell lines [13].
• Additionally, the down-regulation of GIF 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 [14].
• We used an Olympus GIF IT-10 or GIF 2T-10 panendoscope, an Olympus heat probe unit and a 3.2 mm probe (Olympus Co., Taipei, R.O.C.) to treat peptic ulcer bleeding [15].

Biological context of MT3

• MT3 shows apparently different properties and function from MT1 even though they have 70% sequence homology [16].
• 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 [17].
• However, the reaction of the E23K mutant with SNOC exhibited biphasic kinetics and the mutant protein released zinc ions much faster than hMT3 in the initial step, while hMT3 exhibited single kinetic process [18].
• MT-III fulfills unique biological roles in homeostasis of the central nervous system and in the etiology of neuropathological disorders [2].
• Protective effect of metallothionein-III on DNA damage in response to reactive oxygen species [19].

Anatomical context of MT3

• Molecular identifications of HLA-DR4, MT3, and TB21 antigens on HLA-DR4 homozygous B cell lines [20].
• Furthermore, when comparisons were possible, the MT3 pharmacological characteristics were similar to those described in the literature for hamster brain and testis [21].
• 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 [22].

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 [16].
• We suggest the hydroxyl group in human GIF may help stabilize the biologically active conformation [6].
• MT-III was also able to efficiently remove the superoxide anion, which was generated from the xanthine/xanthine oxidase system [19].
• In this study, we show that MT-III 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 [19].
• Results showed that apo-MT-3 and apo-MT-2 have almost equal helical content (approximately 10%) in aqueous buffer, but that MT-3 had slightly higher tendency to form alpha-helical secondary structure in TFE-water mixtures [23].

Physical interactions of MT3

• Results demonstrate that MT-3 binds Zn2+ and Cd2+ ions more weakly than MT-2 but exposes higher metal-binding capacity and plasticity [23].

Regulatory relationships of MT3

• Using an 8-oxoguanine DNA glycosylase (OGG1)-specific siRNAs, we also found that MT-III expression resulted in the suppression of the gamma-radiation-induced 8-oxoG accumulation and mutation in the OGG1-depleted cells [24].
• 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].

Other interactions of MT3

• Metal binding of metallothionein-3 versus metallothionein-2: lower affinity and higher plasticity [23].
• Four major isoforms (MT-I, MT-II, MT-III, and MT-IV) have been identified in mammals [2].
• RESULTS: Reverse transcription-PCR revealed the expression of MT1-, MT2-, MT3-, and MT4-MMP mRNA in all tissues and cell cultures examined [25].
• Although both MT3 and MT4 were significantly associated with RA, there was no significant association between the anticollagen antibodies and any MT type or HLA-DR4 [26].
• In neither the ex vivo expanded precursors nor glycophorin A(+) and CD71(+) cells could MT-1F and MT-3 be detected [27].

Analytical, diagnostic and therapeutic context of MT3

• We constructed a series of human GIF mutants at site 5, and characterized their biochemical properties 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 MT-3 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 [18].
• Molecular characterization of MT3 antigens by two-dimensional gel electrophoresis, NH2-terminal amino acid sequence analysis, and southern blot analysis [28].
• 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 [28].

References