ASCORBATE OFFSETS THE INHIBITORY EFFECT OF INOSITOL PHOSPHATES ON IRON UPTAKE AND TRANSPORT BY CACO-2 CELLS

Differentiated monolayer cultures of Caco-2 human Intestinal cells wer e used as a model to examine interactions between various dietary fact ors related to the intestinal uptake and absorption of nonheme Fe. Cac o-2 cells accumulated 91-98 pmol Fe/mg protein from uptake buffer cont aining 12 nmol of Fe(III)-nitrilotriacetate during a l-hr incubation a t 37 degrees C. Addition of a 10-fold molar excess of inositol hexapho sphate (IP6) and its lesser phosphorylated derivatives (IP3, IP4, and IP5) decreased cellular uptake and transport of Fe from the lumenal co mpartment. Addition of ascorbic acid (AA) to the solution containing I Ps stimulated Fe uptake and transport in a manner dependent upon the r atio of AA to IP and inversely proportional to the degree of phosphory lation of inositol (i.e., IP3 > IP4 > IP5 > IP6). A mixture of essenti al amino acids had minimal impact on Fe uptake in either the absence o r presence of ins. Cellular acquisition of Fe from solutions containin g IPs was further enhanced by simultaneous addition of essential amino acids and AA. The stimulatory influence of ascorbic acid on Fe uptake from solutions containing ins was associated with an increase in the level of ferrous ion. These data further support the usefulness of Cac o-2 cells as a model for Investigating the effects of various dietary factors on mineral bioavailability.