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Activation of rat and human organic anion transporter 1 and 3 by transcription factor B‐cell CLL/lymphoma 6 (BCL6)
Author(s) -
Henjakovic Maja,
Wegner Waja,
Burckhardt Birgitta C.,
Burckhardt Gerhard
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.912.20
Subject(s) - organic anion transporter 1 , biology , promoter , microbiology and biotechnology , transcription factor , gene expression , gene , transporter , biochemistry
In rat kidneys, organic anion transporter 1 (Oat1) and Oat3 are male‐dominant and testosterone‐dependently expressed. Sex‐differences in the secretion of several drugs known to be substrates of human OAT1 and OAT3 suggest a male‐dominant expression of these transporters also in humans. The aim of this study was to identify the regulators of sex‐dependent rat Oat1 and Oat3 transcription and the effect of these regulators on human OAT1 and OAT3 promoters. RNA was isolated from renal cortical slices of four adult rats per sex. Expression profiling was done using SurePrint G3 rat GE 8×60K microarray. Selected candidate genes were verified using real‐time PCR. Luciferase assays were carried out by transient transfection of opossum kidney (OK) cells with promoter fragments and expression vectors. Our results suggest that the male‐dominant expression of Oat1 and Oat3 is not directly regulated by the testosterone/androgen receptor‐complex. The human OAT1 and OAT3 promoters were also not affected by testosterone. The transcription factor B‐cell CLL/lymphoma 6 (BCL6) was male‐dominantly expressed and activated the promoters of Oat1/Oat3 and OAT1/OAT3, independent of predicted BCL6‐binding sites, possibly mediated by the interaction with other transcription factors. BCL6 constitutes a promising candidate gene for the sex‐dependent regulation of rat Oat1/Oat3 and human OAT1/OAT3 transcription.