木犀草素促进囊性纤维化跨膜电导调节因子氯离子通道开放

目的 研究木犀草素对依赖于3, 5-环腺苷酸(cAMP) 的囊性纤维化跨膜电导调节因子(CFTR) Cl-通道的激活作用。 方法 利用稳定共表达人CFTR 与一种对卤族元素敏感的荧光绿蛋白突变体(EYFP-H148Q) 的Fischer 大鼠甲状腺(FRT) 细胞模型, 测定木犀草素对CFTR 介导的I-内流速度。 结果 木犀草素能够以剂量依赖的方式激活CFTR 的I-转运, 其对CFTR Cl-通道的激活效应具有作用迅速、可逆的特点。木犀草素在发挥激活作用时依赖于腺苷环化酶激动剂Forskolin的存在, 其单独与细胞孵育不提高细胞内cAMP 的水平。 结论 发现了木犀草素能够以剂量依赖方式激活CFTR, 并且初步确定了木犀草素通过直接与CFTR 结合发挥作用。

Luteolin activates the cystic fibrosis transmembrane conductance regulator chloride channel

AIM: To investigate the activation effect of luteolin on cAMP-dependent cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. METHODS: A stable transfected epithelial cell line coexpression human CFTR and a green fluorescent protein mutant with ultra-high halide sensitivity (YFP-H148Q) were used to determine CFTR-mediated iodide influx rate. RESULTS: Luteolin increased dose-dependently CFTR-mediated iodide influx.The activity was rapid, reversible and Forskolin-dependent. Luteolin had additive effect with Forskolin mixture and did not elevate intracellular cAMP concentration wirhout Forskolin. CONCLUSION: The study identified luteolin could dose-dependently activate CFTR and provided that luteolin acted by combining with CFTR directly.