Cyanidin increases the expression of Mg 2+ transport carriers mediated by the activation of PPARα in colonic epithelial MCE301 cells

Abstract

Mg 2+ deficiency may be involved in lifestyle-related diseases, including hypertension, cardiovascular diseases, and diabetes mellitus. Dietary Mg 2+ is absorbed in the intestine mediated through transcellular and paracellular pathways. However, there is little research into what factors upregulate Mg 2+ absorption. We searched for food constituents that can increase the expression levels of Mg 2+ transport carriers using mouse colonic epithelial MCE301 cells. Cyanidin, an anthocyanidin found in black beans and berries, increased the mRNA levels of Mg 2+ transport carriers including transient receptor potential melastatin 6 (TRPM6) channel and cyclin M4 (CNNM4). The cyanidin-induced elevation of Mg 2+ 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 Mg 2+ 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 Mg 2+ indicator, showed that Mg 2+ influx and efflux from the cells were enhanced by cyanidin, and which were inhibited by GW6471. Furthermore, cyanidin increased paracellular Mg 2+ flux without affecting transepithelial electrical resistance. We suggest that cyanidin increases intestinal Mg 2+ absorption mediated by the elevation of TRPM6 and CNNM4 expression, and may constitute a phytochemical that can improve Mg 2+ deficiency.