Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0084 Transporter Info
Gene Name SLC12A3
Transporter Name Thiazide-sensitive sodium-chloride cotransporter
Gene ID
6559
UniProt ID
P55017
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Mycotoxins

  Aflatoxin B1

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Aflatoxin B1 results in increased methylation of SLC12A3 intron [9]

Regulation Mechanism

 Transcription Factor Info

  aflatoxin B2

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 aflatoxin B2 results in increased methylation of SLC12A3 intron [9]

Regulation Mechanism

 Transcription Factor Info

Chemical Compound

  aristolochic acid I

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 aristolochic acid I results in increased expression of SLC12A3 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  benzo(e)pyrene

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 benzo(e)pyrene results in increased methylation of SLC12A3 intron [9]

Regulation Mechanism

 Transcription Factor Info

  bisphenol A

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 bisphenol A co-treated with Fulvestrant results in increased methylation of SLC12A3 gene [12]

Regulation Mechanism

 Transcription Factor Info

  Fulvestrant

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 bisphenol A co-treated with Fulvestrant results in increased methylation of SLC12A3 gene [12]

Regulation Mechanism

 Transcription Factor Info

  Hydralazine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Hydralazine co-treated with Valproic Acid results in increased expression of SLC12A3 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  Methapyrilene

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Methapyrilene results in increased methylation of SLC12A3 intron [9]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenite

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 sodium arsenite results in decreased expression of SLC12A3 mRNA [7]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 sodium arsenite results in increased expression of SLC12A3 mRNA [14]

Regulation Mechanism

 Transcription Factor Info

  Succimer

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Succimer co-treated with Magnetite Nanoparticles results in decreased expression of SLC12A3 mRNA [15]

Regulation Mechanism

 Transcription Factor Info

  sulforaphane

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 sulforaphane results in decreased expression of SLC12A3 mRNA [8]

Regulation Mechanism

 Transcription Factor Info

  Valproic Acid

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Hydralazine co-treated with Valproic Acid results in increased expression of SLC12A3 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Valproic Acid results in increased methylation of SLC12A3 gene [16]

Regulation Mechanism

 Transcription Factor Info

Carcinogen

  Arsenic

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Arsenic affects the methylation of SLC12A3 gene [11]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Zidovudine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Zidovudine inhibits the expression of SLC12A3 [1]

  Urethane

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Urethane inhibits the expression of SLC12A3 [2]

  Metolazone

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Metolazone blocks the activity of SLC12A3 [3]

  Polythiazide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Polythiazide blocks the activity of SLC12A3 [3]

  Bendroflumethiazide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Bendroflumethiazide blocks the activity of SLC12A3 [3], [4]

  Trichlormethiazide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Trichlormethiazide inhibits the activity of SLC12A3 [5]

Drug in Phase 3 Trial

  Sulforafan

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sulforafan inhibits the expression of SLC12A3 [8]

Drug in Phase 1 Trial

  Sodium arsenite

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sodium arsenite inhibits the expression of SLC12A3 [7]

Natural Product

  Coal Ash

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Coal Ash increases the expression of SLC12A3 [6]
References
1 Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23.
2 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
3 The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon. J Clin Invest. 2001 Jul;108(2):215-22.
4 DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
5 CUL3 gene analysis enables early intervention for pediatric pseudohypoaldosteronism type II in infancy. Pediatr Nephrol. 2013 Sep;28(9):1881-4.
6 Endothelial effects of emission source particles: acute toxic response gene expression profiles. Toxicol In Vitro. 2009 Feb;23(1):67-77.
7 Cellular and Molecular Effects of Prolonged Low-Level Sodium Arsenite Exposure on Human Hepatic HepaRG Cells. Toxicol Sci. 2018 Apr 1;162(2):676-687.
8 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047.
9 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018;121:214-223.
10 Integration of transcriptomic, proteomic and metabolomic data to reveal the biological mechanisms of AAI injury in renal epithelial cells. Toxicol In Vitro. 2021;70:105054.
11 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106.
12 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
13 A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer. PLoS One. 2006;1(1):e98.
14 A Comprehensive Transcriptomic Analysis of Arsenic-Induced Bladder Carcinogenesis. Cells. 2022;11(15).
15 DMSA-Coated Iron Oxide Nanoparticles Greatly Affect the Expression of Genes Coding Cysteine-Rich Proteins by Their DMSA Coating. Chem Res Toxicol. 2015;28(10):1961-74.
16 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.

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