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Cyanidin Increases the Expression of Mg2+ Transport Carriers Mediated by the Activation of PPARα in Colonic Epithelial MCE301 Cells

1
Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 501-1196, Japan
2
Life Science Research Center, University of Toyama, Toyama 930-0194, Japan
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(3), 641; https://doi.org/10.3390/nu11030641
Received: 14 February 2019 / Revised: 13 March 2019 / Accepted: 13 March 2019 / Published: 16 March 2019
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Abstract

Mg2+ deficiency may be involved in lifestyle-related diseases, including hypertension, cardiovascular diseases, and diabetes mellitus. Dietary Mg2+ is absorbed in the intestine mediated through transcellular and paracellular pathways. However, there is little research into what factors upregulate Mg2+ absorption. We searched for food constituents that can increase the expression levels of Mg2+ transport carriers using mouse colonic epithelial MCE301 cells. Cyanidin, an anthocyanidin found in black beans and berries, increased the mRNA levels of Mg2+ transport carriers including transient receptor potential melastatin 6 (TRPM6) channel and cyclin M4 (CNNM4). The cyanidin-induced elevation of Mg2+ transport carriers was blocked by GW6471, a peroxisome proliferator-activated receptor α (PPARα) inhibitor, but not by PPARγ, PPARδ, and protein kinase A inhibitors. Cyanidin-3-glucoside showed similar results to cyanidin. Cyanidin increased the protein levels of TRPM6 and CNNM4, which were distributed in the apical and lateral membranes, respectively. The nuclear localization of PPARα and reporter activities of Mg2+ transport carriers were increased by cyanidin, which were inhibited by GW6471. The cyanidin-induced elevation of reporter activity was suppressed by a mutation in a PPAR-response element. Fluorescence measurements using KMG-20, an Mg2+ indicator, showed that Mg2+ influx and efflux from the cells were enhanced by cyanidin, and which were inhibited by GW6471. Furthermore, cyanidin increased paracellular Mg2+ flux without affecting transepithelial electrical resistance. We suggest that cyanidin increases intestinal Mg2+ absorption mediated by the elevation of TRPM6 and CNNM4 expression, and may constitute a phytochemical that can improve Mg2+ deficiency. View Full-Text
Keywords: CNNM4; cyanidin; Mg2+ deficiency; PPAR; TRPM6 CNNM4; cyanidin; Mg2+ deficiency; PPAR; TRPM6
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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 (CC BY 4.0).
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Takashina, Y.; Manabe, A.; Tabuchi, Y.; Ikari, A. Cyanidin Increases the Expression of Mg2+ Transport Carriers Mediated by the Activation of PPARα in Colonic Epithelial MCE301 Cells. Nutrients 2019, 11, 641.

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