Lefort Émilie C, Diaconu Bogdan, Bentley Victoria L, Blay Jonathan
Department of Pathology Dalhousie University Halifax NS Canada.
School of Pharmacy University of Waterloo Waterloo ON Canada.
Food Sci Nutr. 2020 Aug 20;8(10):5321-5329. doi: 10.1002/fsn3.1823. eCollection 2020 Oct.
CD26/DPPIV is a cell surface glycoprotein found on cells of the intestinal epithelium including those of the colon. We have previously shown that the dietary flavone apigenin (4',5,7-trihydroxyflavone) upregulates CD26/DPPIV on colon cells. Flavonoids such as apigenin interfere with the action of multiple cellular protein kinases and have the capacity to modulate the cell exterior and its ability to interface with the local environment through different signaling pathways. We show here that the ability of apigenin to upregulate CD26/DPPIV is exerted through and requires the activity of casein kinase 2 (CK2). Inhibitors of CK2 that are distinct from apigenin (emodin, 6-methyl-1,3,8-trihydroxyanthraquinone; TBB, 4,5,6,7-tetrabromobenzotriazole; and DRB, 5,6-dichlorobenzimidazole 1-β-D-ribofuranoside) showed a dose-dependent ability to increase CD26/DPPIV and had the same maximal effect when combined with apigenin at submaximal concentrations. Knockdown of CK2 with siRNA abrogated the ability of apigenin to upregulate CD26/DPPIV. Apigenin treatment of cells had no effect on the levels of CK2 protein, consistent with an inhibition of activity of the enzyme. Apigenin's upregulation of CD26/DPPIV in differentiated human colon epithelial cells depends upon inhibition of CK2 activity. This is a key step in enabling apigenin's ability to regulate the functions of intestinal epithelial cells.
CD26/二肽基肽酶IV（DPPIV）是一种在包括结肠在内的肠道上皮细胞表面发现的糖蛋白。我们之前已经表明，膳食黄酮芹菜素（4',5,7-三羟基黄酮）可上调结肠细胞上的CD26/DPPIV。像芹菜素这样的黄酮类化合物会干扰多种细胞蛋白激酶的作用，并能够通过不同的信号通路调节细胞外表面及其与局部环境相互作用的能力。我们在此表明，芹菜素上调CD26/DPPIV的能力是通过酪蛋白激酶2（CK2）发挥作用的，并且需要CK2的活性。与芹菜素不同的CK2抑制剂（大黄素，6-甲基-1,3,8-三羟基蒽醌；TBB，4,5,6,7-四溴苯并三唑；以及DRB，5,6-二氯苯并咪唑1-β-D-呋喃核糖苷）显示出剂量依赖性增加CD26/DPPIV的能力，并且在与亚最大浓度的芹菜素联合使用时具有相同的最大效果。用小干扰RNA（siRNA）敲低CK2消除了芹菜素上调CD26/DPPIV的能力。芹菜素处理细胞对CK2蛋白水平没有影响，这与该酶活性受到抑制一致。芹菜素在分化的人结肠上皮细胞中对CD26/DPPIV的上调取决于对CK2活性的抑制。这是使芹菜素能够调节肠道上皮细胞功能的关键步骤。
