Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0095 Transporter Info
Gene Name SLC13A5
Transporter Name Sodium-coupled citrate transporter
Gene ID
284111
UniProt ID
Q86YT5
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 SLC13A5 intron [22]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Rifampin

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

  DT Modulation1

 Rifampin increases the expression of SLC13A5 [1]

Regulation Mechanism

 via enhancement of Nuclear receptor subfamily 1 group I member 2 (NR1I2) Transcription Factor Info

Cell System

 Human primary hepatocytes

  Copper Sulfate

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

  DT Modulation1

 Copper Sulfate inhibits the expression of SLC13A5 [2]

  Cisplatin

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

  DT Modulation1

 Cisplatin affects the expression of SLC13A5 [3]

  Decitabine

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

  DT Modulation1

 Decitabine affects the expression of SLC13A5 [3]

  Zidovudine

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

  DT Modulation1

 Zidovudine inhibits the expression of SLC13A5 [4]

  Obeticholic acid

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

  DT Modulation1

 Obeticholic acid inhibits the expression of SLC13A5 [5]

  Valproic Acid

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

  DT Modulation1

 Valproic Acid increases the expression of SLC13A5 [6]

  Testosterone

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

  DT Modulation1

 Testosterone inhibits the expression of SLC13A5 [7]

  Acetaminophen

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

  DT Modulation1

 Acetaminophen inhibits the expression of SLC13A5 [8]

  Cyclosporine

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

  DT Modulation1

 Cyclosporine inhibits the expression of SLC13A5 [9]

Drug in Phase 3 Trial

  Triclosan

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

  DT Modulation1

 Triclosan inhibits the expression of SLC13A5 [16]

Drug in Phase 2 Trial

  Bisphenol A

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

  DT Modulation1

 Bisphenol A affects the expression of SLC13A5 [18]

Drug in Phase 1 Trial

  Quercetin

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

  DT Modulation1

 Quercetin inhibits the expression of SLC13A5 [10]

Investigative Drug

  Milchsaure

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

  DT Modulation1

 Milchsaure inhibits the expression of SLC13A5 [17]

Patented Pharmaceutical Agent

  K-7174

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

  DT Modulation1

 K-7174 inhibits the expression of SLC13A5 [12]

Natural Product

  Particulate Matter

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

  DT Modulation1

 Particulate Matter increases the expression of SLC13A5 [19]

  Tobacco Smoke Pollution

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

  DT Modulation1

 Tobacco Smoke Pollution increases the expression of SLC13A5 [20]

  Resveratrol

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

  DT Modulation1

 Plant Extracts co-treated with Resveratrol results in decreased expression of SLC13A5 mRNA [30]

Regulation Mechanism

 Transcription Factor Info

Environmental toxicant

  Polychlorinated dibenzodioxin

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

  DT Modulation1

 Polychlorinated dibenzodioxin affects the expression of SLC13A5 [11]

Carcinogen

  Benzo(a)pyrene

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

  DT Modulation1

 Benzo(a)pyrene inhibits the expression of SLC13A5 [15]

  Arsenic

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

  DT Modulation1

 sodium arsenate results in increased abundance of Arsenic which results in decreased expression of SLC13A5 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

Health and Environmental Toxicant

  Butyraldehyde

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

  DT Modulation1

 Butyraldehyde increases the expression of SLC13A5 [13]

  tris(1,3-dichloro-2-propyl)phosphate

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

  DT Modulation1

 tris(1,3-dichloro-2-propyl)phosphate inhibits the expression of SLC13A5 [14]

Chemical Compound

  DT Modulation1

 SLC13A5 protein results in decreased susceptibility to Cisplatin [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Zidovudine results in increased expression of SLC13A5 mRNA [4]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Valproic Acid affects the expression of SLC13A5 mRNA [31]

Regulation Mechanism

 Transcription Factor Info

  Pentanal

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

  DT Modulation1

 Pentanal increases the expression of SLC13A5 [13]

  DT Modulation1

 Benzo(a)pyrene promotes the reaction AHR protein co-treated with ARNT protein results in increased expression of SLC13A5 mRNA [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene results in increased methylation of SLC13A5 promoter [25]

Regulation Mechanism

 Transcription Factor Info

  3-Hydroxybutyric Acid

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

  DT Modulation1

 SLC13A5 protein results in decreased abundance of 3-Hydroxybutyric Acid [21]

Regulation Mechanism

 Transcription Factor Info

  acetoacetic acid

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

  DT Modulation1

 SLC13A5 protein results in decreased abundance of acetoacetic acid [21]

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 affects the expression of SLC13A5 mRNA [18]

Regulation Mechanism

 Transcription Factor Info

  butyraldehyde

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

  DT Modulation1

 butyraldehyde results in increased expression of SLC13A5 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  Citric Acid

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

  DT Modulation1

 SLC13A5 protein affects the uptake of Citric Acid [26]

Regulation Mechanism

 Transcription Factor Info

  Doxorubicin

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

  DT Modulation1

 SLC13A5 protein results in decreased susceptibility to Doxorubicin [21]

Regulation Mechanism

 Transcription Factor Info

  Estradiol

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

  DT Modulation1

 Estradiol co-treated with TGFB1 protein results in increased expression of SLC13A5 mRNA [27]

Regulation Mechanism

 Transcription Factor Info

  ferrous chloride

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

  DT Modulation1

 ferrous chloride results in decreased expression of SLC13A5 mRNA [28]

Regulation Mechanism

 Transcription Factor Info

  Fluorouracil

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

  DT Modulation1

 SLC13A5 protein results in decreased susceptibility to Fluorouracil [21]

Regulation Mechanism

 Transcription Factor Info

  Fonofos

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

  DT Modulation1

 Fonofos results in increased methylation of SLC13A5 promoter [29]

Regulation Mechanism

 Transcription Factor Info

  K 7174

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

  DT Modulation1

 K 7174 results in decreased expression of SLC13A5 mRNA [12]

Regulation Mechanism

 Transcription Factor Info

  Lactic Acid

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

  DT Modulation1

 Lactic Acid results in decreased expression of SLC13A5 mRNA [17]

Regulation Mechanism

 Transcription Factor Info

  obeticholic acid

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

  DT Modulation1

 obeticholic acid results in decreased expression of SLC13A5 mRNA [5]

Regulation Mechanism

 Transcription Factor Info

  Parathion

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

  DT Modulation1

 Parathion results in increased methylation of SLC13A5 promoter [29]

Regulation Mechanism

 Transcription Factor Info

  pentanal

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

  DT Modulation1

 pentanal results in increased expression of SLC13A5 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenate

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

  DT Modulation1

 sodium arsenate results in increased abundance of Arsenic which results in decreased expression of SLC13A5 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

  Sorafenib

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

  DT Modulation1

 SLC13A5 protein results in decreased susceptibility to Sorafenib [21]

Regulation Mechanism

 Transcription Factor Info

  terbufos

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

  DT Modulation1

 terbufos results in increased methylation of SLC13A5 promoter [29]

Regulation Mechanism

 Transcription Factor Info

  Tetrachlorodibenzodioxin

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

  DT Modulation1

 Tetrachlorodibenzodioxin affects the expression of SLC13A5 mRNA [11]

Regulation Mechanism

 Transcription Factor Info
References
1 SLC13A5 is a novel transcriptional target of the pregnane X receptor and sensitizes drug-induced steatosis in human liver. Mol Pharmacol. 2015 Apr;87(4):674-82.
2 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
3 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003.
4 Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23.
5 Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
6 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.
7 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384.
8 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.
9 Integrative "-Omics" Analysis in Primary Human Hepatocytes Unravels Persistent Mechanisms of Cyclosporine A-Induced Cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
10 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
11 Cross-species comparisons of transcriptomic alterations in human and rat primary hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci. 2012 May;127(1):199-215.
12 A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease. PLoS One. 2013 Sep 27;8(9):e75568.
13 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.
14 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.
15 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
16 Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
17 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
18 Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134.
19 Toxicogenomic study to identify potential signaling alterations related to nasal inflammatory damages induced by diesel exhaust particles in primary human nasal epithelial cells. Toxicol In Vitro. 2020 Dec;69:104994.
20 Integration of transcriptome analysis with pathophysiological endpoints to evaluate cigarette smoke toxicity in an in vitro human airway tissue model. Arch Toxicol. 2021 May;95(5):1739-1761.
21 Comparative proteomic analysis of SLC13A5 knockdown reveals elevated ketogenesis and enhanced cellular toxic response to chemotherapeutic agents in HepG2 cells. Toxicol Appl Pharmacol. 2020;402:115117.
22 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.
23 Effects of Inorganic Arsenic on Human Prostate Stem-Progenitor Cell Transformation, Autophagic Flux Blockade, and NRF2 Pathway Activation. Environ Health Perspect. 2020;128(6):67008.
24 Arylhydrocarbon receptor-dependent mIndy (Slc13a5) induction as possible contributor to benzo[a]pyrene-induced lipid accumulation in hepatocytes. Toxicology. 2015 Nov 4;337:1-9.
25 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
26 Analysis of naturally occurring mutations in the human uptake transporter NaCT important for bone and brain development and energy metabolism. Sci Rep. 2018;8(1):11330.
27 Transforming growth factor beta1 targets estrogen receptor signaling in bronchial epithelial cells. Respir Res. 2018 Aug 30;19(1):160.
28 Adaptive cellular response of the substantia nigra dopaminergic neurons upon age-dependent iron accumulation. Aging Cell. 2022;21(9):e13694.
29 DNA methylation alterations in response to pesticide exposure in vitro. Environ Mol Mutagen. 2012;53(7):542-9.
30 One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69-82.
31 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20.

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