| Summary: | 碩士 === 國防醫學院 === 生物化學研究所 === 99 === In our previous studies, the purified ginsenoside Compound K (CK) and Rg1 were found to enhance and inhibit the steady-state glucose uptake, respectively, in differentiated human intestinal Caco-2 cells. The effect was attributed to altered SGLT-1 gene expression in the cells treated with these compounds and associated with the essential CRE (cAMP response element) motif located in the SGLT-1 promoter. Despite of these studies, the regulatory mechanism of CK and Rg1 on SGLT-1 expression remains to be clarified. In this study, specific signaling kinase inhibitors were used in western and Q-PCR analysis to find out the signaling pathways involved in the action of these compounds. We found that the EGFR, PI3K, p38, and JNK signaling pathways are involved in the CK-mediated increase of CREB phosphorylation and SGLT-1 gene expression. The effect of Rg1 was found to be reversed by p38 inhibitor, suggesting the involvement of p38 pathway in Rg1-mediated inhibition of CREB phosphorylation and SGLT-1 gene expression. In addition to CK, we also showed that the epidermal growth factor (EGF) increased glucose uptake, CREB phosphorylation, and SGLT-1 gene expression. The effect of EGF was shown to be mediated through EGFR and p38 pathways in the Caco-2 cells. Further studies demonstrated the involvement of EGFR (epidermal growth factor receptor) in the action of ginsenoside CK and Rg1, as CK and Rg1 were found to modulate both EGFR and ErbB2 protein and phosphorylation levels in the cells. The signaling kinases involved in the CK- or Rg1-mediated modulation of EGFR activity were also examined. In summary, we elucidated the signaling mechanism of ginsenoside CK and Rg1 involved in the regulation of SGLT-1 expression in the differentiated human intestinal Caco-2 cells. These findings are important in understanding the pharmacological properties and potential applications of ginseng and ginsenosides.
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