Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0418)
DME Name Glutamine synthetase (GLUL), Homo sapiens DME Info
UniProt ID
GLNA_HUMAN
EC Number    EC: 6.3.1.2     (Click to Show/Hide the Complete EC Tree)
Ligase
Carbon-nitrogen ligase
Amide synthase
EC: 6.3.1.2
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)
                  Acute Toxic Substance Click to Show/Hide the Full List of Xenobiotics:        4 Xenobiotics
                              Cadmium Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01503   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Cadmium up-regulates the expression of DME GLUL [1]
                              Formaldehyde Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01305   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Formaldehyde inhibits the expression of DME GLUL [2]
                              Paraquat Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01422   XEOTIC Info Gene Form Protein
                                 Classification Acute Toxic Substance
                                 DME Modulation Paraquat inhibits the drug-metabolizing activity of DME GLUL [3]
                              Uranium Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00964   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Uranium inhibits the expression of DME GLUL [4]
                  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 GLUL [5]
                              Sodium bichromate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01024   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Sodium bichromate inhibits the expression of DME GLUL [6]
                  Environmental Pollutant Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Sodium arsenate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01023   XEOTIC Info Gene Form Protein
                                 Classification Environmental Pollutant
                                 DME Modulation Sodium arsenate inhibits the drug-metabolizing activity of DME GLUL [7]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Mixture Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Tobacco smoke pollution Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00821   XEOTIC Info Gene Form mRNA
                                 Classification Natural Mixture
                                 DME Modulation Tobacco smoke pollution inhibits the expression of DME GLUL [8], [9]
                              Vitallium Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01511   XEOTIC Info Gene Form mRNA
                                 Classification Natural Mixture
                                 DME Modulation Vitallium up-regulates the expression of DME GLUL [10]
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              4-oxoretinoic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01154   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation 4-oxoretinoic acid up-regulates the expression of DME GLUL [11]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      15 Xenobiotics
                              Acetaminophen Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00217   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Acetaminophen inhibits the expression of DME GLUL [12], [13]
                              Alitretinoin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00167   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Alitretinoin up-regulates the expression of DME GLUL [11]
                              Arsenic trioxide Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00339   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Arsenic trioxide up-regulates the expression of DME GLUL [14]
                              Avobenzone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00411   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Avobenzone up-regulates the expression of DME GLUL [15]
                              Calcitriol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00184   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Calcitriol inhibits the expression of DME GLUL [16]
                              Cyclosporine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00241   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cyclosporine inhibits the expression of DME GLUL [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 GLUL [18]
                              Doxorubicin hydrochloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00292   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Doxorubicin hydrochloride inhibits the expression of DME GLUL [19]
                              Estradiol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00090   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Estradiol up-regulates the expression of DME GLUL [20]
                              Hydroquinone Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00430   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Hydroquinone inhibits the expression of DME GLUL [21]
                              Indomethacin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00047   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Indomethacin inhibits the expression of DME GLUL [22]
                              Isotretinoin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00186   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Isotretinoin up-regulates the expression of DME GLUL [11]
                              Leflunomide Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00053   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Leflunomide up-regulates the expression of DME GLUL [23]
                              Tretinoin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00253   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Tretinoin inhibits the drug-metabolizing activity of DME GLUL [24]
                              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 GLUL [25]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Genistein Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00557   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Genistein inhibits the expression of DME GLUL [26]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Dihydrotestosterone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00536   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Dihydrotestosterone up-regulates the expression of DME GLUL [27]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              N-butyrylglucosamine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01392   XEOTIC Info Gene Form Protein
                                 Classification Investigative Agent
                                 DME Modulation N-butyrylglucosamine induces the drug-metabolizing activity of DME GLUL [28]
References
1 Using expression profiling to understand the effects of chronic cadmium exposure on MCF-7 breast cancer cells. PLoS One. 2013 Dec 20;8(12):e84646.
2 Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
3 Ozone inactivates cyclooxygenase in human tracheal epithelial cells without altering PGHS-2 mRNA or protein. Am J Physiol. 1997 May;272(5 Pt 1):L879-87.
4 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.
5 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
6 Arsenicnduced BRCA1 CpG promoter methylation is associated with the downregulation of ERalpha and resistance to tamoxifen in MCF7 breast cancer cells and mouse mammary tumor xenografts. Int J Oncol. 2019 Mar;54(3):869-878.
7 The effect of milk thistle (Silybum marianum) and its main flavonolignans on CYP2C8 enzyme activity in human liver microsomes. Chem Biol Interact. 2017 Jun 1;271:24-29.
8 Assessment of a 72-hour repeated exposure to Swedish snus extract and total particulate matter from 3R4F cigarette smoke on gingival organotypic cultures. Food Chem Toxicol. 2019 Mar;125:252-270.
9 Assessment of the impact of aerosol from a potential modified risk tobacco product compared with cigarette smoke on human organotypic oral epithelial cultures under different exposure regimens. Food Chem Toxicol. 2018 May;115:148-169.
10 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
11 Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
12 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
13 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
14 Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
15 A long-wave UVA filter avobenzone induces obesogenic phenotypes in normal human epidermal keratinocytes and mesenchymal stem cells. Arch Toxicol. 2019 Jul;93(7):1903-1915.
16 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
17 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
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 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
20 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
21 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
22 Anti-inflammatory agent indomethacin reduces invasion and alters metabolism in a human breast cancer cell line. Neoplasia. 2007 Mar;9(3):222-35.
23 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
24 Retinoic acid antagonizes basal as well as coal tar and glucocorticoid-induced cytochrome P4501A1 expression in human skin. Carcinogenesis. 1995 Mar;16(3):519-24.
25 Histone deacetylase inhibitor valproic acid promotes the differentiation of human induced pluripotent stem cells into hepatocyte-like cells. PLoS One. 2014 Aug 1;9(8):e104010.
26 Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
27 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
28 A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. Drug Metab Dispos. 2008 Aug;36(8):1689-97.

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