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.
Highlights
Magnesium ions (Mg2+ ) play an important role in the regulation of various physiological functions.Over 300 enzymes, including those involved with oxidative phosphorylation and glycolysis, requireMg2+ for their activity
We found that cyanidin and cyanidin-3G increased transient receptor potential melastatin 6 (TRPM6) and CNNM4 expression in colonic MCE301 cells (Figures 1 and 2)
We suggest that cyanidin up-regulates the transcriptional activities of TRPM6 and CNNM4 genes mediated by the nuclear trafficking of peroxisome proliferator-activated receptor α (PPARα) and its binding to PPAR response elements (PPREs) of the promoter region
Summary
Magnesium ions (Mg2+ ) play an important role in the regulation of various physiological functions.Over 300 enzymes, including those involved with oxidative phosphorylation and glycolysis, requireMg2+ for their activity. Magnesium ions (Mg2+ ) play an important role in the regulation of various physiological functions. Chronic Mg2+ deficiency may be one of the causes of lifestyle-related diseases such as hypertension, cardiovascular diseases, and diabetes mellitus [1,2,3]. Mg2+ is necessary to protect individuals from physical and mental stresses [4,5]. Mg2+ deficiency due to reduced dietary intake in healthy people may be rare. Many people are exposed to excessive stress in their social environment, and such stress is thought to be increasing and limiting to health complications. Mg2+ has the capability to relieve tension stress. High fat and energy diets may lead to defects in Mg2+ intake. Individuals under excessive stress and with an unbalanced diet may have a higher
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