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Int. J. Mol. Sci. 2014, 15(1), 958-976; doi:10.3390/ijms15010958
Article

Genistein Induces Increase in Fluid pH, Na+ and HCO3 Concentration, SLC26A6 and SLC4A4 (NBCe1)-B Expression in the Uteri of Ovariectomized Rats

1,†
, 1,†
, 2
, 3
 and 1,†,*
1 Department of Physiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur 50603, Malaysia 2 Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur 50603, Malaysia 3 Department of Anatomy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 24 November 2013 / Revised: 8 December 2013 / Accepted: 29 December 2013 / Published: 10 January 2014
(This article belongs to the Section Bioinorganic Chemistry)
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Abstract

Genistein has been reported to stimulate luminal HCO3 secretion. We hypothesized that genistein mediates this effect via SLC26A6 and SLC4A4 (NBCe1) transporters. Our study aimed to: investigate changes in uterine fluid pH, Na+ and HCO3 concentration and expression of uterine SLC26A6 and NBCe1 under genistein effect. Ovariectomized adult female rats received 25, 50 and 100 mg/kg/day genistein for a week with and without ICI 182780. A day after the last injection, in vivo uterine perfusion was performed to collect uterine fluid for Na+, HCO3 and pH determination. The animals were then sacrificed and uteri were removed for mRNA and protein expression analyses. SLC26A6 and NBCe1-A and NBCe1-B distribution were visualized by immunohistochemistry (IHC). Genistein at 50 and 100 mg/kg/day stimulates uterine fluid pH, Na+ and HCO3 concentration increase. Genistein at 100 mg/kg/day up-regulates the expression of SLC26A6 and SLC4A4 mRNA, which were reduced following concomitant ICI 182780 administration. In parallel, SLC26A6 and NBCe1-B protein expression were also increased following high dose genistein treatment and were localized mainly at the apical membrane of the luminal epithelia. SLC26A6 and NBCe1-B up-regulation by genistein could be responsible for the observed increase in the uterine fluid pH, Na+ and HCO3 concentration under this condition.
Keywords: genistein; SLC26A6; SLC4A4; uterine fluid genistein; SLC26A6; SLC4A4; uterine fluid
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Chinigarzadeh, A.; Kasim, N.F.; Muniandy, S.; Kassim, N.M.; Salleh, N. Genistein Induces Increase in Fluid pH, Na+ and HCO3 Concentration, SLC26A6 and SLC4A4 (NBCe1)-B Expression in the Uteri of Ovariectomized Rats. Int. J. Mol. Sci. 2014, 15, 958-976.

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