Publication: Hepcidin and 1,25(OH)<inf>2</inf>D<inf>3</inf>effectively restore Ca<sup>2+</sup>transport in β-thalassemic mice: Reciprocal phenomenon of Fe<sup>2+</sup>and Ca<sup>2+</sup>absorption
Issued Date
2016-07-01
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ISSN
15221555
01931849
01931849
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2-s2.0-84983797974
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Physiology - Endocrinology and Metabolism. Vol.311, No.1 (2016), E214-E223
Suggested Citation
Kamonshanok Kraidith, Saovaros Svasti, Jarinthorn Teerapornpuntakit, Jim Vadolas, Rattana Chaimana, Sarawut Lapmanee, Panan Suntornsaratoon, Nateetip Krishnamra, Suthat Fucharoen, Narattaphol Charoenphandhu Hepcidin and 1,25(OH)<inf>2</inf>D<inf>3</inf>effectively restore Ca<sup>2+</sup>transport in β-thalassemic mice: Reciprocal phenomenon of Fe<sup>2+</sup>and Ca<sup>2+</sup>absorption. American Journal of Physiology - Endocrinology and Metabolism. Vol.311, No.1 (2016), E214-E223. doi:10.1152/ajpendo.00067.2016 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/42987
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Hepcidin and 1,25(OH)<inf>2</inf>D<inf>3</inf>effectively restore Ca<sup>2+</sup>transport in β-thalassemic mice: Reciprocal phenomenon of Fe<sup>2+</sup>and Ca<sup>2+</sup>absorption
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Abstract
© 2016 the American Physiological Society. Previously, β-thalassemia, an inherited anemic disorder with iron overload caused by loss-of-function mutation of β-globin gene, has been reported to induce osteopenia and impaired whole body calcium metabolism, but the pathogenesis of aberrant calcium homeostasis remains elusive. Herein, we investigated how β-thalassemia impaired intestinal calcium absorption and whether it could be restored by administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or hepcidin, the latter of which was the liver-derived antagonist of intestinal iron absorption. The results showed that, in hemizygous β-globin knockout (BKO) mice, the duodenal calcium transport was lower than that in wild-type littermates, and severity was especially pronounced in female mice. Both active and passive duodenal calcium fluxes in BKO mice were found to be less than those in normal mice. This impaired calcium transport could be restored by 7-day 1,25(OH)2D3treatment. The 1,25(OH)2D3-induced calcium transport was diminished by inhibitors of calcium transporters, e.g., L-type calcium channel, NCX1, and PMCA1b, as well as vesicular transport inhibitors. Interestingly, the duodenal calcium transport exhibited an inverse correlation with transepithelial iron transport, which was markedly enhanced in thalassemic mice. Thus, 3-day subcutaneous hepcidin injection and acute direct hepcidin exposure in the Ussing chamber were capable of restoring the thalassemia-associated impairment of calcium transport; however, the positive effect of hepcidin on calcium transport was completely blocked by proteasome inhibitors MG132 and bortezomib. In conclusion, both 1,25(OH)2D3and hepcidin could be used to alleviate the β-thalassemia-associated impairment of calcium absorption. Therefore, our study has shed light on the development of a treatment strategy to rescue calcium dysregulation in β-thalassemia.