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Cyanidin Increases the Expression of Mg<sup>2+</sup> Transport Carriers Mediated by the Activation of PPARα in Colonic Epithelial MCE301 Cells

Takashina, Yui, Manabe, Aya, Tabuchi, Yoshiaki, Ikari, Akira
Nutrients 2019 v.11 no.3
absorption, black beans, cAMP-dependent protein kinase, cyanidin, cyclins, diabetes mellitus, electrical resistance, epithelium, fluorescence, food composition, hypertension, intestines, magnesium, messenger RNA, mice, mutation, peroxisome proliferator-activated receptor alpha, peroxisome proliferator-activated receptor gamma, protein content, small fruits
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 &alpha; (PPAR&alpha;) inhibitor, but not by PPAR&gamma;, PPAR&delta;, 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 PPAR&alpha; 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.