Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0385 Transporter Info
Gene Name SLC4A4
Transporter Name Electrogenic sodium bicarbonate cotransporter 1
Gene ID
8671
UniProt ID
Q9Y6R1
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Benzo(a)pyrene affects the methylation of SLC4A4 5' UTR [29]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene results in decreased methylation of SLC4A4 promoter [29]

Regulation Mechanism

 Transcription Factor Info

  abrine

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

  DT Modulation1

 abrine results in decreased expression of SLC4A4 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

  antibiotic G 418

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

  DT Modulation1

 antibiotic G 418 results in increased expression of SLC4A4 protein mutant form [10]

Regulation Mechanism

 Transcription Factor Info

  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 decreased expression of SLC4A4 mRNA [26]

Regulation Mechanism

 Transcription Factor Info

  bicalutamide

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

  DT Modulation1

 bicalutamide results in decreased expression of SLC4A4 mRNA [2]

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 decreased methylation of SLC4A4 gene [30]

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 decreased expression of SLC4A4 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  CGP 52608

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

  DT Modulation1

 CGP 52608 promotes the reaction RORA protein binds to SLC4A4 gene [31]

Regulation Mechanism

 Transcription Factor Info

  FR900359

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

  DT Modulation1

 FR900359 affects the phosphorylation of SLC4A4 protein [32]

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 decreased methylation of SLC4A4 gene [30]

Regulation Mechanism

 Transcription Factor Info

  methyleugenol

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

  DT Modulation1

 methyleugenol results in decreased expression of SLC4A4 mRNA [20]

Regulation Mechanism

 Transcription Factor Info

  nickel sulfate

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

  DT Modulation1

 nickel sulfate results in decreased expression of SLC4A4 mRNA [33]

Regulation Mechanism

 Transcription Factor Info

  N-Nitrosopyrrolidine

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

  DT Modulation1

 N-Nitrosopyrrolidine results in decreased expression of SLC4A4 mRNA [20]

Regulation Mechanism

 Transcription Factor Info

  Palmitic Acid

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

  DT Modulation1

 Palmitic Acid results in decreased expression of SLC4A4 mRNA [34]

Regulation Mechanism

 Transcription Factor Info

  pirinixic acid

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

  DT Modulation1

 pirinixic acid binds to and results in increased activity of PPARA protein which results in increased expression of SLC4A4 mRNA [35]

Regulation Mechanism

 Transcription Factor Info

  Selenium

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

  DT Modulation1

 Selenium results in decreased expression of SLC4A4 mRNA [11]

Regulation Mechanism

 Transcription Factor Info

  Silicon Dioxide

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

  DT Modulation1

 Silicon Dioxide analog results in decreased expression of SLC4A4 mRNA [36]

Regulation Mechanism

 Transcription Factor Info

  Sodium

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

  DT Modulation1

 SLC4A4 protein results in increased transport of Sodium [10]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenite

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

  DT Modulation1

 sodium arsenite affects the methylation of SLC4A4 gene [37]

Regulation Mechanism

 Transcription Factor Info

  Sodium Bicarbonate

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

  DT Modulation1

 SLC4A4 protein results in increased transport of Sodium Bicarbonate [10]

Regulation Mechanism

 Transcription Factor Info

  trichostatin A

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

  DT Modulation1

 trichostatin A results in increased expression of SLC4A4 mRNA [5]

Regulation Mechanism

 Transcription Factor Info

  triphenyl phosphate

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

  DT Modulation1

 triphenyl phosphate affects the expression of SLC4A4 mRNA [38]

Regulation Mechanism

 Transcription Factor Info

  Vanadates

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

  DT Modulation1

 Vanadates results in increased expression of SLC4A4 mRNA [33]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Bicalutamide

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

  DT Modulation1

 Bicalutamide inhibits the expression of SLC4A4 [2]

  Tretinoin

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

  DT Modulation1

 Tretinoin increases the expression of SLC4A4 [3]

  Zoledronic Acid

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

  DT Modulation1

 Zoledronic Acid inhibits the expression of SLC4A4 [4]

  Valproic Acid

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

  DT Modulation1

 Valproic Acid increases the expression of SLC4A4 [5]

  Doxorubicin

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

  DT Modulation1

 Doxorubicin inhibits the expression of SLC4A4 [6]

  Temozolomide

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

  DT Modulation1

 Temozolomide inhibits the expression of SLC4A4 [7]

  Cyclosporine

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

  DT Modulation1

 Cyclosporine inhibits the expression of SLC4A4 [8]

  Acetaminophen

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

  DT Modulation1

 Acetaminophen inhibits the expression of SLC4A4 [9]

Drug in Phase 3 Trial

  Vitamin E

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

  DT Modulation1

 Vitamin E inhibits the expression of SLC4A4 [11]

  Triclosan

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

  DT Modulation1

 Triclosan inhibits the expression of SLC4A4 [18]

Drug in Phase 1 Trial

  Dihydrotestosterone

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

  DT Modulation1

 Dihydrotestosterone increases the expression of SLC4A4 [16]

  Trichostatin A

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

  DT Modulation1

 Trichostatin A increases the expression of SLC4A4 [22]

Drug in Preclinical Test

  (+)-JQ1

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

  DT Modulation1

 (+)-JQ1 inhibits the expression of SLC4A4 [14]

Investigative Drug

  N-cyanosulphonamide S0859

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

  DT Modulation1

 The synthetic compound N-cyanosulphonamide S0859 inhibits the activity of SLC4A4 (IC50 = 9 microM) [1]

Cell System

 Xenopus laevis oocytes-NBCe1

Patented Pharmaceutical Agent

  Geneticin

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

  DT Modulation1

 Geneticin increases the expression of SLC4A4 [10]

  GSK-J4

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

  DT Modulation1

 GSK-J4 inhibits the expression of SLC4A4 [15]

Natural Product

  Selenium nanoparticles

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

  DT Modulation1

 Selenium nanoparticles inhibits the expression of SLC4A4 [11]

  Particulate Matter

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

  DT Modulation1

 Particulate Matter inhibits the expression of SLC4A4 [17]

  Methyleugenol

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

  DT Modulation1

 Methyleugenol inhibits the expression of SLC4A4 [20]

  Tobacco Smoke Pollution

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

  DT Modulation1

 Tobacco Smoke Pollution inhibits the expression of SLC4A4 [21]

Mycotoxins

  Aflatoxin B1

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

  DT Modulation1

 Aflatoxin B1 inhibits the expression of SLC4A4 [12]

  DT Modulation2

 Aflatoxin B1 results in decreased methylation of SLC4A4 gene [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Aflatoxin B1 results in decreased methylation of SLC4A4 intron [25]

Regulation Mechanism

 Transcription Factor Info

  Aflatoxin M1

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

  DT Modulation1

 Aflatoxin M1 inhibits the expression of SLC4A4 [19]

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 SLC4A4 [20]

  Arsenic

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

  DT Modulation1

 Arsenic affects the methylation of SLC4A4 gene [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Arsenic results in increased methylation of SLC4A4 gene [28]

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 inhibits the expression of SLC4A4 [13]
References
1 Inhibition of monocarboxylate transporter by N-cyanosulphonamide S0859. Eur J Pharmacol. 2015 Sep 5;762:344-9.
2 Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell lines. J Pharm Pharmacol. 2005 Jan;57(1):83-92.
3 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
4 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
5 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
6 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.
7 Temozolomide induces activation of Wnt/beta-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278.
8 Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel. Toxicol Appl Pharmacol. 2014 Sep 1;279(2):163-72.
9 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
10 G418-mediated ribosomal read-through of a nonsense mutation causing autosomal recessive proximal renal tubular acidosis. Am J Physiol Renal Physiol. 2008 Sep;295(3):F633-41.
11 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
12 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.
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 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
15 Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of natural killer cells. J Biol Chem. 2018 Feb 16;293(7):2422-2437.
16 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.
17 Transcriptional profiling of human bronchial epithelial cell BEAS-2B exposed to diesel and biomass ultrafine particles. BMC Genomics. 2018 Apr 27;19(1):302.
18 Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
19 Transcriptome analysis revealed that aflatoxin M1 could cause cell cycle arrest in differentiated Caco-2 cells. Toxicol In Vitro. 2019 Sep;59:35-43.
20 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297.
21 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.
22 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
23 Integration of transcriptomics, proteomics and metabolomics data to reveal the biological mechanisms of abrin injury in human lung epithelial cells. Toxicol Lett. 2019;312:1-10.
24 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
25 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.
26 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.
27 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.
28 Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh. Environ Health Perspect. 2015;123(1):64-71.
29 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
30 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
31 Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
32 Protein Kinase Signaling Networks Driven by Oncogenic Gq/11 in Uveal Melanoma Identified by Phosphoproteomic and Bioinformatic Analyses. Mol Cell Proteomics. 2023;22(11):100649.
33 Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer. Metallomics. 2012 Aug;4(8):784-93.
34 Palmitic Acid Induced a Dedifferentiation Profile at the Transcriptome Level: A Collagen Synthesis but no Triglyceride Accumulation in Hepatocyte-Like Cells Derived From Human-Induced Pluripotent Stem Cells Cultivated Inside Organ on a Chip. J Appl Toxicol. 2025;45(3):460-471.
35 Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human. PLoS One. 2009;4(8):e6796.
36 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;16(1):315.
37 Microarray dataset of transient and permanent DNA methylation changes in HeLa cells undergoing inorganic arsenic-mediated epithelial-to-mesenchymal transition. Data Brief. 2017;13:6-9.
38 Association between Organophosphate Ester Exposure and Insulin Resistance with Glycometabolic Disorders among Older Chinese Adults 60-69 Years of Age: Evidence from the China BAPE Study. Environ Health Perspect. 2023;131(4):47009.

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