Modulation of human Caco-2 intestinal epithelial cell phenotype by protein kinase C inhibitors
Modulation of human Caco-2 intestinal epithelial cell phenotype by protein kinase C inhibitors
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DOI：
10.1006/cbir.1995.1045
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发表时间：
1995-12-01
影响因子：
3.9
通讯作者：
Hong, F
中科院分区：
文献类型：
--
作者：
Basson, MD;Hong, F
蛋白激酶C(PKC)亚型在结肠肿瘤和肠道粘膜暴露于营养物质时会发生变化。我们评价了蛋白激酶C抑制剂星形孢子素和钙磷蛋白C对人Caco-2肠上皮细胞增殖、运动和分化的影响。单层扩张法测定细胞的运动能力，人工底物消化法测定刷状缘酶二肽基二肽酶(DPDD)和碱性磷酸酶(AP)。星形孢菌素(0.03-1.0 ng/ml)和钙磷蛋白C(10(-12)M-10(-4)M)呈剂量依赖性地抑制单层扩张和AP，但刺激DPDD。丝裂霉素C增殖阻断后，细胞的增殖也受到抑制，但各抑制剂对细胞活力、AP和DPDD的影响均被保留，提示这些作用是增殖独立的。PKC抑制剂独立地抑制人肠道Caco-2上皮细胞的运动、AP和增殖，但选择性地刺激小肠分化标记物DPDD。PKC可能参与了小肠上皮细胞分化的调控。
Protein kinase C (PKC) isoforms are altered in colon tumors and upon exposure of intestinal mucosa to nutrients. We evaluated the effects of the PKC inhibitors staurosporine and calphostin C on human Caco-2 intestinal epithelial proliferation, motility and differenfiation. Motility was quantified by monolayer expansion and the brush border enzymes dipeptidyl dipeptidase (DPDD) and alkaline phosphatase (AP) by synthetic substrate digestion. Staurosporine (0.03-1.0 ng/ml) and calphostin C (10(-12)M-10(-4) M) dose-dependently inhibited monolayer expansion and AP but stimulated DPDD. Proliferation was also inhibited but the effects of each inhibitor on motility, AP, and DPDD were preserved after mitomycin C proliferative blockade, suggesting that these effects were proliferation-indepentent. PKC inhibitors independently inhibit motility, AP and proliferation in human intestinal Caco-2 epithelial cells, but selectively stimulate the small intestinal differentiation marker DPDD. PKC may regulate small intestinal epithelial differentiation.