Sex-dependent expression of Oat3 (Slc22a8) and Oat1 (Slc22a6) proteins in murine kidneys
Document Type
Article
Original Publication Date
2013
Journal/Book/Conference Title
American Journal of Physiology - Renal Physiology
Volume
304
Issue
8
First Page
F1114
Last Page
F1126
DOI of Original Publication
10.1152/ajprenal.00201.2012
Date of Submission
October 2015
Abstract
In the mouse kidney, organic anion transporter 3 (mOat3, Slc22a8) was previously localized to the basolateral membrane (BLM) of proximal tubule (PT), thick ascending limb of Henle, macula densa, distal tubule, and cortical collecting duct. However, the specificity of anti-Oat3 antibodies (Oat3-Ab) used in these studies was not properly verified. Moreover, the sex-dependent expression of mOat3, and of the functionally similar transporter mOat1 (Slc22a6), in the mouse kidney has been studied at mRNA level, whereas their protein expression is poorly documented. Here we investigated 1) specificity of Oat3-Abs by using Oat3knockout (KO) mice, 2) cell localization of renal mOat3 with a specific mOat3-Ab, 3) sex-dependent expression of renal mOat3 and mOat1 proteins, and 4) hormone(s) responsible for observed sex differences. As previously shown, an Oat3-Ab against the rat protein stained the BLM of various nephron segments in wild-type (WT) mice, but the same staining pattern was noted along the nephron of Oat3 KO mice. However, the mOat3-Ab exclusively stained the BLM of PT in WT mice, where it colocalized with the mOat1 protein, whereas no staining of Oat3 protein was noted in the kidney of Oat3 KO mice. The expression of mOat3 protein was lower in male mice, upregulated by castration, and downregulated by testosterone treatment. The expression of mOat1 protein was stronger in males, downregulated by castration, and upregulated by testosterone treatment. Thus, at the protein level, mOat3 and mOat1 exhibit sex-dependent expression with an opposite pattern; mOat3 is female dominant due to androgen inhibition, while mOat1 is male dominant due to androgen stimulation.
Rights
Copyright © 2013 the American Physiological Society
Is Part Of
VCU Pharmaceutics Publications
Comments
Originally published at doi:10.1152/ajprenal.00201.2012
PMCID: PMC3625837