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Title: Na<sup>+</sup>/H<sup>+</sup>exchanger 3 inhibitor diminishes hepcidin-enhanced duodenal calcium transport in hemizygous β-globin knockout thalassemic mice
Authors: Narattaphol Charoenphandhu
Kamonshanok Kraidith
Kornkamon Lertsuwan
Chanakarn Sripong
Panan Suntornsaratoon
Saovaros Svasti
Nateetip Krishnamra
Kannikar Wongdee
Mahidol University
Burapha University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Mar-2017
Citation: Molecular and Cellular Biochemistry. Vol.427, No.1-2 (2017), 201-208
Abstract: © 2016, Springer Science+Business Media New York. Recent investigation has shown that the liver-derived iron-regulating hormone, hepcidin, can potentiate intestinal calcium absorption in hemizygous β-globin knockout thalassemic (BKO) mice. Since the upregulation of Fe2+and H+cotransporter, divalent metal transporter (DMT)-1, has been shown to correlate with thalassemia-induced intestinal calcium absorption impairment, the inhibition of the apical Na+/H+exchanger (NHE)-3 that is essential for cytoplasmic pH regulation and transepithelial sodium absorption was hypothesized to negatively affect hepcidin action. Herein, the positive effect of hepcidin on the duodenal calcium transport was evaluated using Ussing chamber technique. The results showed that BKO mice had lower absorptive surface area and duodenal calcium transport than wild-type mice. Besides, paracellular transport of zinc in BKO mice was compromised. Hepcidin administration completely restored calcium transport. Since this hepcidin action was totally abolished by inhibitors of the basolateral calcium transporters, Na+/Ca2+exchanger (NCX1) and plasma membrane Ca2+-ATPase (PMCA1b), the enhanced calcium flux potentially occurred through the transcellular pathway rather than paracellular pathway. Interestingly, the selective NHE3 inhibitor, 100 nM tenapanor, markedly inhibited hepcidin-enhanced calcium transport. Accordingly, hepcidin is one of the promising therapeutic agents for calcium malabsorption in β-thalassemia. It mainly stimulates the transcellular calcium transport across the duodenal epithelium in an NHE3-dependent manner.
ISSN: 15734919
Appears in Collections:Scopus 2016-2017

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