Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0094)
DME Name Metallothionein-1A (MT1A), Homo sapiens DME Info
UniProt ID
MT1A_HUMAN
EC Number    EC: 1.8.5.1     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
Sulfur donor oxidoreductase
Quinone acceptor oxidoreductase
EC: 1.8.5.1
Lineage    Species: Homo sapiens     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Interactome
Interactions between Xenobiotics and DME (XEOTIC)
      Fungicide(s), Herbicide(s) or Insecticide(s)
                  Herbicide Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Atrazine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00969   XEOTIC Info Gene Form mRNA
                                 Classification Herbicide
                                 DME Modulation Atrazine up-regulates the expression of DME MT1A [1]
      Health or Environmental Toxicant(s)
                  Acute Toxic Substance Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Cadmium Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01503   XEOTIC Info Gene Form Protein
                                 Classification Acute Toxic Substance
                                 DME Modulation Cadmium induces the drug-metabolizing activity of DME MT1A [2]
                              Chloropicrin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01247   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Chloropicrin up-regulates the expression of DME MT1A [3]
                              Ochratoxin A Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01407   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Ochratoxin A up-regulates the expression of DME MT1A [4]
                  Biotoxin Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Azaspiracid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01502   XEOTIC Info Gene Form mRNA
                                 Classification Marine Algal Toxin
                                 DME Modulation Azaspiracid up-regulates the expression of DME MT1A [5]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Benzo(a)pyrene Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00898   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Benzo(a)pyrene inhibits the expression of DME MT1A [6]
                              Aflatoxin B1 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00806   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen-mycotoxin
                                 DME Modulation Aflatoxin B1 up-regulates the expression of DME MT1A [7], [8]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Mixture Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Dust Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01284   XEOTIC Info Gene Form mRNA
                                 Classification Natural Mixture
                                 DME Modulation Dust up-regulates the expression of DME MT1A [9]
                              Particulate matter Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00919   XEOTIC Info Gene Form mRNA
                                 Classification Natural Mixture
                                 DME Modulation Particulate matter up-regulates the expression of DME MT1A [10]
                              Tobacco smoke pollution Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00821   XEOTIC Info Gene Form Protein
                                 Classification Natural Mixture
                                 DME Modulation Tobacco smoke pollution inhibits the drug-metabolizing activity of DME MT1A [11]
                  Plant Extract Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Grape seed proanthocyanidins Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00758   XEOTIC Info Gene Form mRNA
                                 Classification Plant Extract
                                 DME Modulation Grape seed proanthocyanidins inhibits the expression of DME MT1A [12]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      14 Xenobiotics
                              Arsenic trioxide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00339   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Arsenic trioxide inhibits the expression of DME MT1A [13]
                              Cisplatin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00334   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cisplatin up-regulates the expression of DME MT1A [14]
                              Copper sulfate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00117   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Copper sulfate up-regulates the expression of DME MT1A [15]
                              Cupric chloride Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00407   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cupric chloride up-regulates the expression of DME MT1A [16]
                              Cytarabine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00097   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cytarabine inhibits the expression of DME MT1A [17]
                              Dexamethasone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00088   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Dexamethasone up-regulates the expression of DME MT1A [18]
                              Dronabinol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00115   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Dronabinol up-regulates the expression of DME MT1A [19]
                              Estradiol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00090   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Estradiol inhibits the expression of DME MT1A [20]
                              Nitroprusside Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00398   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Nitroprusside up-regulates the expression of DME MT1A [21]
                              Progesterone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00094   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Progesterone up-regulates the expression of DME MT1A [22]
                              Valproic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00029   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Valproic acid up-regulates the expression of DME MT1A [23]
                              Benzoic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00447   XEOTIC Info Gene Form mRNA
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Benzoic acid up-regulates the expression of DME MT1A [24]
                              Silver nitrate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00511   XEOTIC Info Gene Form mRNA
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Silver nitrate up-regulates the expression of DME MT1A [25]
                              Zinc sulfate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00460   XEOTIC Info Gene Form mRNA
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Zinc sulfate up-regulates the expression of DME MT1A [26]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Diphenylcyclopropenone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00612   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Diphenylcyclopropenone up-regulates the expression of DME MT1A [24]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        5 Xenobiotics
                              AM-80 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00622   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2/3
                                 DME Modulation AM-80 up-regulates the expression of DME MT1A and leads to increasing the drug-metabolizing activity of this enzyme [27]
                              Salicylic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00546   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2/3
                                 DME Modulation Salicylic acid up-regulates the expression of DME MT1A [28]
                              Arecoline Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00578   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Arecoline up-regulates the expression of DME MT1A [29]
                              Genistin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00645   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Genistin up-regulates the expression of DME MT1A [30]
                              Hydroxytamoxifen Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00634   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Hydroxytamoxifen up-regulates the expression of DME MT1A [31]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Sodium arsenite Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00632   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Sodium arsenite induces the drug-metabolizing activity of DME MT1A [32], [33]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              (+)-JQ1 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00723   XEOTIC Info Gene Form mRNA
                                 Classification Drug in Preclinical Study
                                 DME Modulation (+)-JQ1 inhibits the expression of DME MT1A [34], [35]
                              K-7174 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01348   XEOTIC Info Gene Form mRNA
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation K-7174 inhibits the expression of DME MT1A [36]
      Other Chemical Compound(s) or Element(s)
                  Cosmetic Additive Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Hydroxycitronellal Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01334   XEOTIC Info Gene Form mRNA
                                 Classification Cosmetic Additive
                                 DME Modulation Hydroxycitronellal up-regulates the expression of DME MT1A [24]
                  Chemical Compound Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Cupric oxide Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00840   XEOTIC Info Gene Form mRNA
                                 Classification Chemical Compound
                                 DME Modulation Cupric oxide up-regulates the expression of DME MT1A [37], [15]
References
1 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
2 Increased levels of metallothionein in placenta of smokers. Toxicology. 2005 Mar 1;208(1):133-9.
3 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
4 Ezrin inhibition up-regulates stress response gene expression. J Biol Chem. 2016 Jun 17;291(25):13257-70.
5 Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells. Toxicol In Vitro. 2018 Feb;46:102-112.
6 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
7 Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):176-87.
8 Zinc inhibits aflatoxin B1-induced cytotoxicity and genotoxicity in human hepatocytes (HepG2 cells). Food Chem Toxicol. 2016 Jun;92:17-25.
9 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
10 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
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12 Dietary catechins and procyanidins modulate zinc homeostasis in human HepG2 cells. J Nutr Biochem. 2011 Feb;22(2):153-63.
13 Arsenic trioxide (ATO) influences the gene expression of metallothioneins in human glioblastoma cells. Biol Trace Elem Res. 2012 Dec;149(3):331-9.
14 Expression pattern of cisplatin-induced metallothionein isoforms in squamous cell carcinoma. Anticancer Res. 2003 Jan-Feb;23(1A):299-303.
15 Effects of different sources of copper on Ctr1, ATP7A, ATP7B, MT and DMT1 protein and gene expression in Caco-2 cells. J Trace Elem Med Biol. 2014 Jul;28(3):344-50.
16 Gene expression profiling of liver cells after copper overload in vivo and in vitro reveals new copper-regulated genes. J Biol Inorg Chem. 2007 May;12(4):495-507.
17 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
18 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
19 Gene expression changes in human small airway epithelial cells exposed to Delta9-tetrahydrocannabinol. Toxicol Lett. 2005 Aug 14;158(2):95-107.
20 Human drug metabolism genes in parathion-and estrogen-treated breast cells. Int J Mol Med. 2007 Dec;20(6):875-81.
21 Mitochondrial uncoupling reveals a novel therapeutic opportunity for p53-defective cancers. Nat Commun. 2018 Sep 26;9(1):3931.
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24 A new in vitro method for identifying chemical sensitizers combining peptide binding with ARE/EpRE-mediated gene expression in human skin cells. Cutan Ocul Toxicol. 2010 Sep;29(3):171-92.
25 High-throughput, quantitative assessment of the effects of low-dose silica nanoparticles on lung cells: grasping complex toxicity with a great depth of field. BMC Genomics. 2015 Apr 18;16:315.
26 Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
27 Methylated pentavalent arsenic metabolites are bifunctional inducers, as they induce cytochrome P450 1A1 and NAD(P)H:quinone oxidoreductase through AhR- and Nrf2-dependent mechanisms. Free Radic Biol Med. 2014 Feb;67:171-87.
28 A comprehensive evaluation of anti-diabetic drugs on nuclear receptor PXR platform. Toxicol In Vitro. 2019 Oct;60:347-358.
29 The upregulation of metallothionein-1 expression in areca quid chewing-associated oral squamous cell carcinomas. Oral Oncol. 2008 Feb;44(2):180-6.
30 Water-soluble genistin glycoside isoflavones up-regulate antioxidant metallothionein expression and scavenge free radicals. J Agric Food Chem. 2006 May 31;54(11):3819-26.
31 Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J. 2009 Mar 4;28(5):523-32.
32 Increased clozapine plasma concentrations and side effects induced by smoking cessation in 2 CYP1A2 genotyped patients. Ther Drug Monit. 2005 Aug;27(4):539-43.
33 Toxicity of wood smoke particles in human A549 lung epithelial cells: the role of PAHs, soot and zinc. Arch Toxicol. 2016 Dec;90(12):3029-3044.
34 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
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37 Molecular responses of human lung epithelial cells to the toxicity of copper oxide nanoparticles inferred from whole genome expression analysis. ACS Nano. 2011 Dec 27;5(12):9326-38.

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