Expression of organic cation transporter 1 (OCT1): unique patterns of indirect regulation by nuclear receptors and hepatospecific gene regulation
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F16%3A10328923" target="_blank" >RIV/00216208:11160/16:10328923 - isvavai.cz</a>
Result on the web
<a href="http://www.tandfonline.com/doi/full/10.1080/03602532.2016.1188936" target="_blank" >http://www.tandfonline.com/doi/full/10.1080/03602532.2016.1188936</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/03602532.2016.1188936" target="_blank" >10.1080/03602532.2016.1188936</a>
Alternative languages
Result language
angličtina
Original language name
Expression of organic cation transporter 1 (OCT1): unique patterns of indirect regulation by nuclear receptors and hepatospecific gene regulation
Original language description
The organic cation transporter 1 (OCT1) is the dominant carrier of organic cationic drugs and some positively charged endogenous compounds into hepatocytes. OCT1 has unique expression pattern. It has the highest expression among drug transporters in normal human hepatocytes with large interindividual variability, but it has negligible expression in other tissues or their tumors. Nowadays, it is clear that the regulation of SLC22A1 gene encoding OCT1 transporter is rather complex and that transactivation with hepatocyte nuclear factor 4alpha (HNF4alpha) and CCAAT-enhancer-binding protein (C/EBPs) transcription factors as well as epigenetic regulation contribute to its unique hepatocyte-specific expression pattern. Unfortunately, species- and tissue-specific regulation of OCT1 and its orthologs as well as significant down-regulation in most immortalized cell lines hamper the study of SLC22A1 gene regulation. In the current review, we summarize our current understanding of human OCT1 transporter hepatic gene regulation and we propose potential post-transcriptional regulation by predicted miRNAs. We also discuss in detail recent findings on indirect regulation of the transporter via farnesoid X receptor (FXR), glucocorticoid receptor and pregnane X (PXR) receptor, which point out to potential novel mechanisms of xenobiotic-transporting and drug-metabolizing proteins regulation in the human liver as well as to potentially novel drug-drug interaction mechanisms. We also propose that comprehensive understanding of mechanisms of SLC22A1 gene regulation could direct research for other drug transporters and drug-metabolizing enzymes highly expressed in hepatocytes and controlled by HNF4alpha or other liver-enriched transcription factors.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
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Result continuities
Project
<a href="/en/project/GBP303%2F12%2FG163" target="_blank" >GBP303/12/G163: Centre of drug-dietary supplements interactions and nutrigenetics</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Drug Metabolism Reviews
ISSN
0360-2532
e-ISSN
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Volume of the periodical
48
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
20
Pages from-to
139-158
UT code for WoS article
000380135800001
EID of the result in the Scopus database
2-s2.0-84977563176