Molecular Aspects of intestinal calcium absorption

DÍAZ DE BARBOZA G; GUIZZARDI S; TOLOSA DE TALAMONI N

WORLD JOURNAL OF GASTROENTEROLOGY

W J G PRESS

Lugar: Beijing; Año: 2015 vol. 21 p. 7142 - 7154

1007-9327

The intestinal Ca2+ absorption is a crucial physiological process to maintain bone mineralization and Ca2+ homeostasis. It occurs through transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca2+ across the brush border membranes (BBM) of enterocytes through the epithelial Ca2+ channels TRPV6, TRPV5 and Cav1.3, followed by the Ca2+ movement from the BBM to the basolateral membranes by binding proteins with high Ca2+affinity such as CB9k, and finally the Ca2+ extrusion into the blood. The plasma membrane Ca2+ ATP-ase or PMCA1b and sodium calcium exchanger or NCX1 are mainly involved in the Ca2+ exit out of the enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b because both molecules co-localize and interact. The paracellular pathway consists of the Ca2+ transport through transmembrane proteins of tight junction structures such as Claudins 2, 12 and 15. There is evidence of a crosstalk between the transcellular and the paracellular pathways in the intestinal Ca2+ transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways inhibiting the intestinal Ca2+ absorption. The normalization of the redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid and melatonin return the intestinal Ca2+ transport to control values. Calcitriol or 1,25(OH)2D3 is the major controlling hormone of the intestinal Ca2+ transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone and glucocorticoids apparently also regulate the Ca2+ transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)2D3 production or both. Different physiological conditions as growth, pregnancy, lactation and aging adjust the intestinal Ca2+ absorption according to the Ca2+ demands. The knowledge of the molecular details of the intestinal Ca2+ absorption could lead to develop nutritional and medical strategies to optimize the efficiency of intestinal Ca2+ absorption and to prevent osteoporosis and other pathologies related to Ca2+ metabolism.