title: Molecular aspects of intestinal calcium absorption.
abstract: Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) 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 Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2+) absorption could lead to the development of nutritional and medical strategies for optimizing the efficiency of intestinal Ca(2+) absorption and preventing osteoporosis and other pathologies related to Ca(2+) metabolism.
authors.affiliation: Gabriela Diaz de Barboza, Solange Guizzardi, Nori Tolosa de Talamoni, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Diaz de Barboza
authors.affiliation: Gabriela Diaz de Barboza, Solange Guizzardi, Nori Tolosa de Talamoni, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina.
authors.forename: Solange
authors.initials: S
authors.lastname: Guizzardi
authors.affiliation: Gabriela Diaz de Barboza, Solange Guizzardi, Nori Tolosa de Talamoni, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina.
authors.forename: Nori
authors.initials: N
authors.lastname: Tolosa de Talamoni
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D017136:Ion Transport
chemical_list: D027682:Cation Transport Proteins; D002118:Calcium
keywords: 1,25(OH)2D3; Aging; Estrogen; Intestinal Ca2+ absorption; Lactation; PTH; Paracellular route; Pregnancy; Prolactin; Transcellular pathway