دورية أكاديمية
Cytochrome P450 and UDP-Glucuronosyltransferase Expressions, Activities, and Induction Abilities in 3D-Cultured Human Renal Proximal Tubule Epithelial Cells.
| العنوان: | Cytochrome P450 and UDP-Glucuronosyltransferase Expressions, Activities, and Induction Abilities in 3D-Cultured Human Renal Proximal Tubule Epithelial Cells. |
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| المؤلفون: | Hashiba S; Drug Metabolism and Toxicology (S.H., Ma.N., I.Y., T.F., Mi.N.) and Pharmaceutical and Health Sciences (H.A.), Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University, Kanazawa, Japan (Ma.N., T.F., Mi.N.); R&D Department, Precision Engineering Center, Industrial Division, Nikkiso Co., Ltd., Kanazawa, Japan (E.T., M.K., Y.J.); and Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co. Ltd., Kobe, Japan (N.I.)., Nakano M; Drug Metabolism and Toxicology (S.H., Ma.N., I.Y., T.F., Mi.N.) and Pharmaceutical and Health Sciences (H.A.), Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University, Kanazawa, Japan (Ma.N., T.F., Mi.N.); R&D Department, Precision Engineering Center, Industrial Division, Nikkiso Co., Ltd., Kanazawa, Japan (E.T., M.K., Y.J.); and Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co. Ltd., Kobe, Japan (N.I.) mnakano@staff.kanazawa-u.ac.jp nmiki@p.kanazawa-u.ac.jp., Yokoseki I; Drug Metabolism and Toxicology (S.H., Ma.N., I.Y., T.F., Mi.N.) and Pharmaceutical and Health Sciences (H.A.), Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University, Kanazawa, Japan (Ma.N., T.F., Mi.N.); R&D Department, Precision Engineering Center, Industrial Division, Nikkiso Co., Ltd., Kanazawa, Japan (E.T., M.K., Y.J.); and Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co. Ltd., Kobe, Japan (N.I.)., Takahashi E; Drug Metabolism and Toxicology (S.H., Ma.N., I.Y., T.F., Mi.N.) and Pharmaceutical and Health Sciences (H.A.), Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University, Kanazawa, Japan (Ma.N., T.F., Mi.N.); R&D Department, Precision Engineering Center, Industrial Division, Nikkiso Co., Ltd., Kanazawa, Japan (E.T., M.K., Y.J.); and Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co. Ltd., Kobe, Japan (N.I.)., Kondo M; Drug Metabolism and Toxicology (S.H., Ma.N., I.Y., T.F., Mi.N.) and Pharmaceutical and Health Sciences (H.A.), Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University, Kanazawa, Japan (Ma.N., T.F., Mi.N.); R&D Department, Precision Engineering Center, Industrial Division, Nikkiso Co., Ltd., Kanazawa, Japan (E.T., M.K., Y.J.); and Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co. Ltd., Kobe, Japan (N.I.)., Jimbo Y; Drug Metabolism and Toxicology (S.H., Ma.N., I.Y., T.F., Mi.N.) and Pharmaceutical and Health Sciences (H.A.), Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University, Kanazawa, Japan (Ma.N., T.F., Mi.N.); R&D Department, Precision Engineering Center, Industrial Division, Nikkiso Co., Ltd., Kanazawa, Japan (E.T., M.K., Y.J.); and Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co. Ltd., Kobe, Japan (N.I.)., Ishiguro N; Drug Metabolism and Toxicology (S.H., Ma.N., I.Y., T.F., Mi.N.) and Pharmaceutical and Health Sciences (H.A.), Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University, Kanazawa, Japan (Ma.N., T.F., Mi.N.); R&D Department, Precision Engineering Center, Industrial Division, Nikkiso Co., Ltd., Kanazawa, Japan (E.T., M.K., Y.J.); and Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co. Ltd., Kobe, Japan (N.I.)., Arakawa H; Drug Metabolism and Toxicology (S.H., Ma.N., I.Y., T.F., Mi.N.) and Pharmaceutical and Health Sciences (H.A.), Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University, Kanazawa, Japan (Ma.N., T.F., Mi.N.); R&D Department, Precision Engineering Center, Industrial Division, Nikkiso Co., Ltd., Kanazawa, Japan (E.T., M.K., Y.J.); and Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co. Ltd., Kobe, Japan (N.I.)., Fukami T; Drug Metabolism and Toxicology (S.H., Ma.N., I.Y., T.F., Mi.N.) and Pharmaceutical and Health Sciences (H.A.), Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University, Kanazawa, Japan (Ma.N., T.F., Mi.N.); R&D Department, Precision Engineering Center, Industrial Division, Nikkiso Co., Ltd., Kanazawa, Japan (E.T., M.K., Y.J.); and Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co. Ltd., Kobe, Japan (N.I.)., Nakajima M; Drug Metabolism and Toxicology (S.H., Ma.N., I.Y., T.F., Mi.N.) and Pharmaceutical and Health Sciences (H.A.), Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University, Kanazawa, Japan (Ma.N., T.F., Mi.N.); R&D Department, Precision Engineering Center, Industrial Division, Nikkiso Co., Ltd., Kanazawa, Japan (E.T., M.K., Y.J.); and Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co. Ltd., Kobe, Japan (N.I.). |
| المصدر: | Drug metabolism and disposition: the biological fate of chemicals [Drug Metab Dispos] 2024 Aug 14; Vol. 52 (9), pp. 949-956. Date of Electronic Publication: 2024 Aug 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Pharmacology and Experimental Therapeutics, etc.] Country of Publication: United States NLM ID: 9421550 Publication Model: Electronic Cited Medium: Internet ISSN: 1521-009X (Electronic) Linking ISSN: 00909556 NLM ISO Abbreviation: Drug Metab Dispos Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Bethesda, Md., etc., American Society for Pharmacology and Experimental Therapeutics, etc.] |
| مواضيع طبية MeSH: | Kidney Tubules, Proximal*/metabolism , Kidney Tubules, Proximal*/cytology , Kidney Tubules, Proximal*/drug effects , Glucuronosyltransferase*/metabolism , Glucuronosyltransferase*/genetics , Epithelial Cells*/metabolism , Epithelial Cells*/drug effects , Cytochrome P-450 Enzyme System*/metabolism , Cytochrome P-450 Enzyme System*/genetics, Humans ; Cells, Cultured ; Enzyme Induction/drug effects ; Cell Line ; Cell Culture Techniques/methods ; RNA, Messenger/metabolism ; RNA, Messenger/genetics |
| مستخلص: | The role of the kidney as an excretory organ for exogenous and endogenous compounds is well recognized, but there is a wealth of data demonstrating that the kidney has significant metabolizing capacity for a variety of exogenous and endogenous compounds that in some cases surpass the liver. The induction of drug-metabolizing enzymes by some chemicals can cause drug-drug interactions and intraindividual variability in drug clearance. In this study, we evaluated the expression and induction of cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT) isoforms in 3D-cultured primary human renal proximal tubule epithelial cells (RPTEC) to elucidate their utility as models of renal drug metabolism. CYP2B6, CYP2E1, CYP3A4, CYP3A5, and all detected UGTs (UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7) mRNA levels in 3D-RPTEC were significantly higher than those in 2D-RPTEC and HK-2 cells and were close to the levels in the human kidney cortex. CYP1B1 and CYP2J2 mRNA levels in 3D-RPTEC were comparable to those in 2D-RPTEC, HK-2 cells, and the human kidney cortex. Midazolam 1'-hydroxylation, trifluoperazine N -glucuronidation, serotonin O -glucuronidation, propofol O -glucuronidation, and morphine 3-glucuronidation in the 3D-RPTEC were significantly higher than the 2D-RPTEC and comparable to those in the HepaRG cells, although bupropion, ebastine, and calcitriol hydroxylations were not different between the 2D- and 3D-RPTEC. Treatment with ligands of the aryl hydrocarbon receptor and farnesoid X receptor induced CYP1A1 and UGT2B4 expression, respectively, in 3D-RPTEC compared with 2D-RPTEC. We provided information on the expression, activity, and induction abilities of P450s and UGTs in 3D-RPTEC as an in vitro human renal metabolism model. SIGNIFICANCE STATEMENT: This study demonstrated that the expression of cytochrome P450s (P450s) and UDP-glucuronosyltransferases (UGTs) in 3D-cultured primary human renal proximal tubule epithelial cells (3D-RPTEC) was higher than those in 2D-cultured primary human renal proximal tubule epithelial cells and HK-2 cells. The results were comparable to that in the human kidney cortex. 3D-RPTEC are useful for evaluating the induction of kidney P450s, UDP-glucuronosyltransferases, and human renal drug metabolism in cellulo. (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.) |
| المشرفين على المادة: | EC 2.4.1.17 (Glucuronosyltransferase) 9035-51-2 (Cytochrome P-450 Enzyme System) 0 (RNA, Messenger) |
| تواريخ الأحداث: | Date Created: 20240612 Date Completed: 20240814 Latest Revision: 20240814 |
| رمز التحديث: | 20240815 |
| DOI: | 10.1124/dmd.124.001685 |
| PMID: | 38866474 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1521-009X |
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| DOI: | 10.1124/dmd.124.001685 |