Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0483 Transporter Info
Gene Name SLC9A3
Transporter Name Sodium/hydrogen exchanger 3
Gene ID
6550
UniProt ID
P48764
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Valproic Acid results in increased methylation of SLC9A3 gene [18]

Regulation Mechanism

 Transcription Factor Info

  3-(2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methylphenyl)-N-isopropylidene-2-methyl-acrylamide dihydrochloride

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

  DT Modulation1

 3-(2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methylphenyl)-N-isopropylidene-2-methyl-acrylamide dihydrochloride results in decreased activity of SLC9A3 protein [9]

Regulation Mechanism

 Transcription Factor Info

  7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

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

  DT Modulation1

 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide results in increased expression of SLC9A3 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  Agent Orange

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

  DT Modulation1

 Defoliants, Chemical results in increased abundance of Agent Orange which results in increased abundance of Tetrachlorodibenzodioxin which results in decreased methylation of SLC9A3 gene [11]

Regulation Mechanism

 Transcription Factor Info

  Benzo(a)pyrene

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

  DT Modulation1

 Benzo(a)pyrene affects the methylation of SLC9A3 intron [13]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene affects the methylation of SLC9A3 promoter [14]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Benzo(a)pyrene results in increased methylation of SLC9A3 5' UTR [14]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation4

 Benzo(a)pyrene results in increased methylation of SLC9A3 exon [14]

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 SLC9A3 intron [13]

Regulation Mechanism

 Transcription Factor Info

  bisphenol A

            2 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 SLC9A3 gene [15]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 bisphenol A results in increased methylation of SLC9A3 gene [15]

Regulation Mechanism

 Transcription Factor Info

  bisphenol S

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

  DT Modulation1

 bisphenol S co-treated with Fulvestrant results in decreased methylation of SLC9A3 gene [15]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 bisphenol S results in decreased methylation of SLC9A3 gene [15]

Regulation Mechanism

 Transcription Factor Info

  Cisplatin

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

  DT Modulation1

 Cisplatin co-treated with jinfukang results in increased expression of SLC9A3 mRNA [7]

Regulation Mechanism

 Transcription Factor Info

  Fulvestrant

            2 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 SLC9A3 gene [15]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 bisphenol S co-treated with Fulvestrant results in decreased methylation of SLC9A3 gene [15]

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 SLC9A3 intron [13]

Regulation Mechanism

 Transcription Factor Info

  NVP-BKM120

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

  DT Modulation1

 sotorasib co-treated with trametinib co-treated with NVP-BKM120 results in decreased expression of SLC9A3 mRNA [16]

Regulation Mechanism

 Transcription Factor Info

  Sodium Chloride

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

  DT Modulation1

 Resveratrol results in increased expression of SLC9A3 protein which results in increased uptake of Sodium Chloride [6]

Regulation Mechanism

 Transcription Factor Info

  sotorasib

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

  DT Modulation1

 sotorasib co-treated with trametinib co-treated with NVP-BKM120 results in decreased expression of SLC9A3 mRNA [16]

Regulation Mechanism

 Transcription Factor Info

  Tetrachlorodibenzodioxin

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

  DT Modulation1

 Defoliants, Chemical results in increased abundance of Agent Orange which results in increased abundance of Tetrachlorodibenzodioxin which results in decreased methylation of SLC9A3 gene [11]

Regulation Mechanism

 Transcription Factor Info

  trametinib

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

  DT Modulation1

 sotorasib co-treated with trametinib co-treated with NVP-BKM120 results in decreased expression of SLC9A3 mRNA [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 SLC9A3 gene [12]

Regulation Mechanism

 Transcription Factor Info

Natural Product

  DT Modulation1

 Plant Extracts co-treated with Resveratrol results in decreased expression of SLC9A3 mRNA [17]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Resveratrol results in increased expression of SLC9A3 protein which results in increased uptake of Sodium Chloride [6]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Dexamethasone

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

  DT Modulation1

 Dexamethasone increases the expression of SLC9A3 [1]

  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 SLC9A3 [2]

  Decitabine

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

  DT Modulation1

 Decitabine increases the expression of SLC9A3 [3]

  Folic Acid

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

  DT Modulation1

 Folic Acid inhibits the expression of SLC9A3 [4]

  Fluorouracil

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

  DT Modulation1

 Fluorouracil inhibits the expression of SLC9A3 [5]

Drug in Phase 3 Trial

  Resveratrol

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

  DT Modulation1

 Resveratrol increases the expression of SLC9A3 [6]

Traditional Medicine

  Jinfukang

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

  DT Modulation1

 Jinfukang increases the expression of SLC9A3 [7]

Acute Toxic Substance

  Acrylamide

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

  DT Modulation1

 Acrylamide inhibits the expression of SLC9A3 [8]
References
1 Dexamethasone increases fluid absorption via Na+/H+ exchanger (NHE) 3 activation in normal human middle ear epithelial cells. Eur J Pharmacol. 2006 Apr 24;536(1-2):12-8.
2 The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
3 Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53.
4 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92.
5 New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids. Arch Toxicol. 2021 Aug;95(8):2691-2718.
6 Role of Na+/H+ exchanger in resveratrol-induced growth inhibition of human breast cancer cells. Med Oncol. 2012 Mar;29(1):25-32.
7 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
8 Acrylamide exposure represses neuronal differentiation, induces cell apoptosis and promotes tau hyperphosphorylation in hESC-derived 3D cerebral organoids. Food Chem Toxicol. 2020 Oct;144:111643.
9 Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron. Am J Physiol Renal Physiol. 2001;281(6):F1117-22.
10 Benzo[a]pyrene diol epoxide stimulates an inflammatory response in normal human lung fibroblasts through a p53 and JNK mediated pathway. Carcinogenesis. 2010;31(6):1149-57.
11 DNA methylation in the adipose tissue and whole blood of Agent Orange-exposed Operation Ranch Hand veterans: a pilot study. Environ Health. 2021;20(1):43.
12 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.
13 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.
14 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
15 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
16 Inhibition of KRAS, MEK and PI3K Demonstrate Synergistic Anti-Tumor Effects in Pancreatic Ductal Adenocarcinoma Cell Lines. Cancers (Basel). 2022;14(18).
17 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.
18 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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