Nucleotide and Nucleoside Supplementation May Morphologically Promote the Differentiation of Human Caco-2 Cells

The effects of nucleotide and nucleoside supplementation on the formation of tight junctions and the expression of microvilli, as indexes of morphological differentiation were studied by using a human colon adenocarcinoma cell line (Caco-2 cells). The forma-tion of tight junctions and the expression of microvilli were evaluated by measuring the transepithelial electrical resistance (TEER) and observing the cell surface under electron mi-croscopic analysis, respectively. To clarify the nutritional significance of human milk nu-cleotides, we used a nucleotide mixture (and a corresponding nucleoside mixture) with a composition similar to that found in human milk. Nucleotides had no effect on TEER, but nucleosides markedly promoted the increase of TEER. When alkaline phosphatase activity in the brush border membrane was enhanced by the addition of triiodothyronine (TIT), nu-cleotides also promoted the increase of TEER. Cytidine and CMP predominant in the mix-ture influenced the increase of TEER materially. Furthermore, an electron microphotograph of the cell surface showed that nucleosides contributed to the expression of microvilli. Thus the results presented in this study suggest that nucleotide and nucleoside supplementation may enhance the morphological differentiation of Caco-2 cells.