Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0086 Transporter Info
Gene Name SLC12A5
Transporter Name Electroneutral potassium-chloride cotransporter 2
Gene ID
57468
UniProt ID
Q9H2X9
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Furosemide inhibits the reaction SLC12A5 protein results in increased import of Thallium [5]

Regulation Mechanism

 Transcription Factor Info

  Benzo(a)pyrene

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

  DT Modulation1

 Benzo(a)pyrene affects the methylation of SLC12A5 promoter [9]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene results in increased methylation of SLC12A5 5' UTR [9]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Benzo(a)pyrene results in increased methylation of SLC12A5 exon [9]

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 promotes the reaction MECP2 protein binds to SLC12A5 promoter [6]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 bisphenol A results in decreased expression of SLC12A5 mRNA [6]

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 SLC12A5 mRNA [7]

Regulation Mechanism

 Transcription Factor Info

  cobaltous chloride

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

  DT Modulation1

 cobaltous chloride results in increased expression of SLC12A5 mRNA [11]

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 SLC12A5 mRNA [12]

Regulation Mechanism

 Transcription Factor Info

  Ethylmaleimide

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

  DT Modulation1

 Ethylmaleimide inhibits the reaction SLC12A5 protein results in increased import of Thallium [5]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Ethylmaleimide results in increased activity of SLC12A5 protein [5]

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 SLC12A5 mRNA [14]

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 SLC12A5 gene [15]

Regulation Mechanism

 Transcription Factor Info

  Staurosporine

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

  DT Modulation1

 Staurosporine inhibits the reaction SLC12A5 protein results in increased import of Thallium [5]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Staurosporine results in increased activity of SLC12A5 protein [5]

Regulation Mechanism

 Transcription Factor Info

  Thallium

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

  DT Modulation1

 ((dihydroindenyl)oxy)alkanoic acid inhibits the reaction SLC12A5 protein results in increased import of Thallium [5]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Ethylmaleimide inhibits the reaction SLC12A5 protein results in increased import of Thallium [5]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Furosemide inhibits the reaction SLC12A5 protein results in increased import of Thallium [5]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation4

 SLC12A5 protein results in increased import of Thallium [5]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation5

 Staurosporine inhibits the reaction SLC12A5 protein results in increased import of Thallium [5]

Regulation Mechanism

 Transcription Factor Info

Pesticide/Insecticide

  Chlorpyrifos

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

  DT Modulation1

 APOE protein alternative form affects the susceptibility to Chlorpyrifos which affects the expression of SLC12A5 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

Natural Product

  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 SLC12A5 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Ivermectin

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

  DT Modulation1

 Ivermectin inhibits the expression of SLC12A5 [1]

  Furosemide

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

  DT Modulation1

 Furosemide inhibits the activity of SLC12A5 [2], [3]

  Reserpine

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

  DT Modulation1

 Reserpine inhibits the activity of SLC12A5 [4]

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 inhibits the expression of SLC12A5 [6]

Drug in Preclinical Test

  AM-2282

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

  DT Modulation1

 AM-2282 increases the activity of SLC12A5 [5]

Investigative Drug

  N-ethylmaleimide

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

  DT Modulation1

 N-ethylmaleimide increases the activity of SLC12A5 [5]

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 SLC12A5 [7]

  Lead

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

  DT Modulation1

 Lead affects the expression of SLC12A5 [8]
References
1 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975.
2 Downregulation of KCC2 following LTP contributes to EPSP-spike potentiation in rat hippocampus. Biochem Biophys Res Commun. 2006 May 19;343(4):1209-15.
3 Chloride homeostasis differentially affects GABA(A) receptor- and glycine receptor-mediated effects on spontaneous circuit activity in hippocampal cell culture. Neurosci Lett. 2006 Oct 2;406(1-2):11-6.
4 Blockade of spinal 5-GABAa receptors differentially reduces reserpine-induced fibromyalgia-type pain in female rats. Eur J Pharmacol. 2019 Jun 7:172443.
5 A thallium transport FLIPR-based assay for the identification of KCC2-positive modulators. J Biomol Screen. 2010 Feb;15(2):177-84.
6 Bisphenol A delays the perinatal chloride shift in cortical neurons by epigenetic effects on the Kcc2 promoter. Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4315-20.
7 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.
8 RNA-Seq of Human Neural Progenitor Cells Exposed to Lead (Pb) Reveals Transcriptome Dynamics, Splicing Alterations and Disease Risk Associations. Toxicol Sci. 2017 Sep 1;159(1):251-265.
9 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
10 Exposure to chlorpyrifos during pregnancy differentially affects social behavior and GABA signaling elements in an APOE- and sex-dependent manner in a transgenic mouse model. Environ Res. 2023;224:115461.
11 Global gene expression profiling in human lung cells exposed to cobalt. BMC Genomics. 2007;8:147.
12 Transforming growth factor beta1 targets estrogen receptor signaling in bronchial epithelial cells. Respir Res. 2018 Aug 30;19(1):160.
13 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.
14 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.
15 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.

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