RNA Editing Enzymes Modulate the Expression of Hepatic CYP2B6, CYP2C8, and Other Cytochrome P450 Isoforms.

Journal

Drug metabolism and disposition: the biological fate of chemicals
ISSN: 1521-009X
Titre abrégé: Drug Metab Dispos
Pays: United States
ID NLM: 9421550

Informations de publication

Date de publication:
06 2019
Historique:
received: 10 02 2019
accepted: 08 04 2019
pubmed: 17 4 2019
medline: 17 4 2019
entrez: 17 4 2019
Statut: ppublish

Résumé

A-to-I RNA editing, the most frequent type of RNA editing in mammals, is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes. Recently, we found that there is a large interindividual variation in the expression of ADAR1 protein in the human livers. In this study, we investigated the possibility that A-to-I RNA editing may modulate the expression of cytochrome P450 (P450), causing interindividual variations in drug metabolism potencies. We found that knockdown of ADAR1 or ADAR2 in HepaRG cells resulted in the decreased expression of CYP2B6 and CYP2C8 mRNA and protein. Knockdown of ADARs significantly decreased the stability of CYP2B6 mRNA but not CYP2C8 mRNA. Luciferase assays revealed that the 3'-untranslated region of CYP2B6 and the promoter region of CYP2C8 would be involved in the decrease in their expression by the knockdown of ADARs. We found that the decreased expression of the hepatocyte nuclear factor 4

Identifiants

DOI: 10.1124/dmd.119.086702 PMID: 30988053
pubmed: 30988053
pii: dmd.119.086702
doi: 10.1124/dmd.119.086702
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

639-647

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.

Auteurs

Kaori Nozaki (K)

Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences (K.N., Ma.N., C.I., T.F., Mi.N.), and WPI Nano Life Science Institute (Ma.N., T.F., Mi.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan.

Masataka Nakano (M)

Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences (K.N., Ma.N., C.I., T.F., Mi.N.), and WPI Nano Life Science Institute (Ma.N., T.F., Mi.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan.

Chika Iwakami (C)

Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences (K.N., Ma.N., C.I., T.F., Mi.N.), and WPI Nano Life Science Institute (Ma.N., T.F., Mi.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan.

Tatsuki Fukami (T)

Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences (K.N., Ma.N., C.I., T.F., Mi.N.), and WPI Nano Life Science Institute (Ma.N., T.F., Mi.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan.

Miki Nakajima (M)

Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences (K.N., Ma.N., C.I., T.F., Mi.N.), and WPI Nano Life Science Institute (Ma.N., T.F., Mi.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan nmiki@p.kanazawa-u.ac.jp.

Classifications MeSH