Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0081)
DME Name Glutathione S-transferase alpha-2 (GSTA2), Homo sapiens DME Info
UniProt ID
GSTA2_HUMAN
EC Number    EC: 2.5.1.18     (Click to Show/Hide the Complete EC Tree)
Transferase
Alkyl/aryl transferase
Alkyl/aryl transferase
EC: 2.5.1.18
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)
      Health or Environmental Toxicant(s)
                  Biotoxin Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Cylindrospermopsin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00905   XEOTIC Info Gene Form mRNA
                                 Classification Cyanotoxin
                                 DME Modulation Cylindrospermopsin inhibits the expression of DME GSTA2 [1]
                              Azaspiracid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01502   XEOTIC Info Gene Form mRNA
                                 Classification Marine Algal Toxin
                                 DME Modulation Azaspiracid inhibits the expression of DME GSTA2 [2]
                  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 GSTA2 [3]
                              Aflatoxin B1 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00806   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen-mycotoxin
                                 DME Modulation Aflatoxin B1 inhibits the expression of DME GSTA2 [4], [5]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Iprodione Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00851   XEOTIC Info Gene Form mRNA
                                 Classification Health and Environmental Toxicant
                                 DME Modulation Iprodione up-regulates the expression of DME GSTA2 [6]
                              Butyraldehyde Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00999   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Butyraldehyde inhibits the expression of DME GSTA2 [7]
                              Diethylhexyl phthalate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01004   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Diethylhexyl phthalate up-regulates the expression of DME GSTA2 [8]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Bilirubin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00877   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation Bilirubin up-regulates the expression of DME GSTA2 [9]
                              Indolo(3,2-B)carbazole Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01343   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation Indolo(3,2-B)carbazole inhibits the expression of DME GSTA2 [3]
                              Isoimperatorin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01554   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation Isoimperatorin up-regulates the expression of DME GSTA2 [10]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:        5 Xenobiotics
                              Copper sulfate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00117   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Copper sulfate inhibits the expression of DME GSTA2 [11]
                              Ketoconazole Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00251   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Ketoconazole inhibits the expression of DME GSTA2 [12]
                              Leflunomide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00053   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Leflunomide inhibits the expression of DME GSTA2 [13]
                              Phenobarbital Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00410   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Phenobarbital inhibits the drug-metabolizing activity of DME GSTA2 [14]
                              Urethane Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00435   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Urethane inhibits the expression of DME GSTA2 [15]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Diethyltoluamide Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00582   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Diethyltoluamide up-regulates the expression of DME GSTA2 [16]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Lactacystin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01362   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2/3
                                 DME Modulation Lactacystin up-regulates the expression of DME GSTA2 [17]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              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 GSTA2 [18]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              MG-132 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01219   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation MG-132 up-regulates the expression of DME GSTA2 [17]
References
1 Cylindrospermopsin induced transcriptional responses in human hepatoma HepG2 cells. Toxicol In Vitro. 2013 Sep;27(6):1809-19.
2 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.
3 Gene expression profiling in Caco-2 human colon cells exposed to TCDD, benzo[a]pyrene, and natural Ah receptor agonists from cruciferous vegetables and citrus fruits. Toxicol In Vitro. 2008 Mar;22(2):396-410.
4 Aflatoxins upregulate CYP3A4 mRNA expression in a process that involves the PXR transcription factor. Toxicol Lett. 2011 Aug 28;205(2):146-53.
5 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.
6 Cytotoxicity and transcriptional activation of stress genes in human liver carcinoma (HepG2) cells exposed to iprodione. Int J Environ Res Public Health. 2004 Mar;1(1):12-20.
7 Integrated analysis of microRNA and mRNA expression profiles highlights aldehyde-induced inflammatory responses in cells relevant for lung toxicity. Toxicology. 2015 Aug 6;334:111-21.
8 Long-term di (2-ethylhexyl)-phthalate exposure promotes proliferation and survival of HepG2 cells via activation of NFB. Toxicol In Vitro. 2017 Aug;42:86-92.
9 Interleukin 1beta inhibits CAR-induced expression of hepatic genes involved in drug and bilirubin clearance. Hepatology. 2004 Oct;40(4):951-60.
10 Potent protective effect of isoimperatorin against aflatoxin B1-inducible cytotoxicity in H4IIE cells: bifunctional effects on glutathione S-transferase and CYP1A. Carcinogenesis. 2006 Dec;27(12):2483-90.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor. Mol Pharmacol. 2006 Jul;70(1):329-39.
13 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
14 Modulation of the endogenous antioxidants paraoxonase-1 and urate by pesticide exposure and genetic variants of xenobiotic-metabolizing enzymes. Food Chem Toxicol. 2013 Nov;61:164-70.
15 Defensive and adverse energy-related molecular responses precede tris (1, 3-dichloro-2-propyl) phosphate cytotoxicity. J Appl Toxicol. 2016 May;36(5):649-58.
16 Impact of environmental chemicals on the transcriptome of primary human hepatocytes: potential for health effects. J Biochem Mol Toxicol. 2016 Aug;30(8):375-95.
17 Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response elementDegradation of Nrf2 by the 26 S proteasome. J Biol Chem. 2003 Feb 14;278(7):4536-41.
18 A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease. PLoS One. 2013 Sep 27;8(9):e75568.

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