Universität zu Köln

Euteneuer, Anna M., Seeger-Nukpezah, Tamina, Nolte, Hendrik and Henjakovic, Maja (2019). Estrogen receptor alpha (ER alpha) indirectly induces transcription of human renal organic anion transporter 1 (OAT1). PHYSIOL. REP., 7 (21). HOBOKEN: WILEY. ISSN 2051-817X

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Abstract

Organic anion transporter 1 (OAT1) is a polyspecific transport protein located in the basolateral membrane of renal proximal tubule cells. OAT1 plays a pivotal role in drug clearance. Adverse drug reactions (ADR) are observed more frequently in women than in men, especially ADR are higher in women for drugs which are known interactors of OAT1. Sex-dependent expression of Oat1 has been observed in rodents with a tendency to male-dominant expression. This study aims at elucidating the transcriptional regulation of human OAT1 and tests the effect of estrogen receptor alpha (ER alpha). Promoter activation of OAT1 was assessed by luciferase assays carried out by Opossum kidney (OK) cells, transiently transfected with promoter constructs of human OAT1 and expression vectors for ER alpha and exposed to 100 nmol/L 17 beta-estradiol. Furthermore, a transcription factor array and proteomic analysis was performed to identify estrogen-induced transcription factors. Human OAT1 was significantly activated by ligand activated ER alpha. However, activation occurred without a direct interaction of ER alpha with the OAT1 promoter. Our data rather show an activation of the transcription factors CCAAT-box-binding transcription factor (CBF) and heterogeneous nuclear ribonucleoprotein K (HNRNPK) by ER alpha, which in turn bind and initiate OAT1 promoter activity. Herewith, we provide novel evidence of estrogen-dependent, transcriptional regulation of polyspecific drug transporters including the estrogen-induced transcription factors CBF and HNRNPK.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Euteneuer, Anna M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Seeger-Nukpezah, Tamina UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Henjakovic, Maja UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-129192
DOI:	10.14814/phy2.14229
Journal or Publication Title:	PHYSIOL. REP.
Volume:	7
Number:	21
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2051-817X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NUCLEAR RIBONUCLEOPROTEIN K; GENE-EXPRESSION; HNRNP-K; SEX-DIFFERENCES; BREAST-CANCER; BINDING; IDENTIFICATION; PROMOTER; ACTIVATION; ADVERSE Multiple languages Physiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12919