Molecularaspectsofintestinalcalciumabsorption

摘要： IntestinalCa2+absorptionisacrucialphysiologicalprocessformaintainingbonemineralizationandCa2+homeostasis.Itoccursthroughthetranscellularandparacellularpathways.Thefirstroutecomprises3steps:theentranceofCa2+acrossthebrushbordermembranes(BBM)ofenterocytesthroughepithelialCa2+channelsTRPV6,TRPV5,andCav1.3;Ca2+movementfromtheBBMtothebasolateralmembranesbybindingproteinswithhighCa2+affinity(suchasCB9k);andCa2+extrusionintotheblood.PlasmamembraneCa2+ATPase(PMCA1b)andsodiumcalciumexchanger(NCX1)aremainlyinvolvedintheexitofCa2+fromenterocytes.Anovelmolecule,the4.1Rprotein,seemstobeapartnerofPMCA1b,sincebothmoleculescolocalizeandinteract.TheparacellularpathwayconsistsofCa2+transportthroughtransmembraneproteinsoftightjunctionstructures,suchasclaudins2,12,and15.ThereisevidenceofcrosstalkbetweenthetranscellularandparacellularpathwaysinintestinalCa2+transport.Whenintestinaloxidativestressistriggered,thereisadecreaseintheexpressionofseveralmoleculesofbothpathwaysthatinhibitintestinalCa2+absorption.Normalizationofredoxstatusintheintestinewithdrugssuchasquercetin,ursodeoxycholicacid,ormelatoninreturnintestinalCa2+transporttocontrolvalues.Calcitriol[1,25(OH)2D3]isthemajorcontrollinghormoneofintestinalCa2+transport.Itincreasesthegeneandproteinexpressionofmostofthemoleculesinvolvedinbothpathways.PTH,thyroidhormones,estrogens,prolactin,growthhormone,andglucocorticoidsapparentlyalsoregulateCa2+transportbydirectaction,indirectmechanismmediatedbytheincreaseofrenal1,25(OH)2D3production,orboth.Differentphysiologicalconditions,suchasgrowth,pregnancy,lactation,andaging,adjustintestinalCa2+absorptionaccordingtoCa2+demands.BetterknowledgeofthemoleculardetailsofintestinalCa2+absorptioncouldleadtothedevelopmentofnutritionalandmedicalstrategiesforoptimizingtheefficiencyofintestinalCa2+absorptionandpreventingosteoporosisandotherpathologiesrelatedtoCa2+metabolism. ... （共13頁）