Butyrate increases apical membrane CFTR but reduces chloride secretion in MDCK cells
Butyrate increases apical membrane CFTR but reduces chloride secretion in MDCK cells
复制标题
DOI：
10.1152/ajprenal.1999.277.2.f271
复制
发表时间：
1999-08-01
影响因子：
4.2
通讯作者：
Stanton, BA
中科院分区：
文献类型：
--
作者：
Moyer, BD;Loffing-Cueni, D;Stanton, BA
丁酸钠及其衍生物是用于治疗遗传性疾病的有用治疗剂，所述遗传性疾病包括尿素循环障碍、镰状细胞病、地中海贫血和可能的囊性纤维化（CF）。丁酸盐通过刺激Delta F508囊性纤维化跨膜传导调节因子（Delta F508-CFTR）基因表达和增加质膜中Delta F508-CFTR的量，部分恢复CF上皮细胞中cAMP激活的Cl-分泌。由于丁酸盐对肾上皮细胞Cl-分泌的影响尚未报道，我们研究了慢性丁酸盐处理（15-18 h）对稳定转染的MDCK细胞中CFTR融合绿色荧光蛋白（GFP-CFTR）的功能、表达和定位的影响。我们报告说，丁酸钠减少跨MDCK细胞的Cl-分泌，但增加顶端膜GFP-CFTR表达25倍，并增加顶端膜Cl-电流30倍。虽然丁酸盐也使Na-K-ATP酶蛋白表达增加两倍，但药物使Na-K-ATP酶活性降低了55%。我们的研究结果表明，丁酸盐通过降低Na-K-ATP酶的活性来抑制cAMP刺激的MDCK细胞的Cl-分泌。
Sodium butyrate and its derivatives are useful therapeutic agents for the treatment of genetic diseases including urea cycle disorders, sickle cell disease, thalassemias, and possibly cystic fibrosis (CF). Butyrate partially restores cAMP-activated Cl- secretion in CF epithelial cells by stimulating Delta F508 cystic fibrosis transmembrane conductance regulator (Delta F508-CFTR) gene expression and increasing the amount of Delta F508-CFTR in the plasma membrane. Because the effect of butyrate on Cl- secretion by renal epithelial cells has not been reported, we examined the effects of chronic butyrate treatment (15-18 h) on the function, expression, and localization of CFTR fused to the green fluorescent protein (GFP-CFTR) in stably transfected MDCK cells. We report that sodium butyrate reduced Cl- secretion across MDCK cells, yet increased apical membrane GFP-CFTR expression 25-fold and increased apical membrane Cl- currents 30-fold. Although butyrate also increased Na-K-ATPase protein expression twofold, the drug reduced the activity of the Na-K-ATPase by 55%. Our findings suggest that butyrate inhibits cAMP-stimulated Cl- secretion across MDCK cells in part by reducing the activity of the Na-K-ATPase.