Abnormal glutathione transport in cystic fibrosis airway epithelia
Abnormal glutathione transport in cystic fibrosis airway epithelia
复制标题
DOI：
10.1152/ajplung.1999.277.1.l113
复制
发表时间：
1999-07-01
影响因子：
4.9
通讯作者：
Forman, HJ
中科院分区：
文献类型：
--
作者：
Gao, L;Kim, KJ;Forman, HJ
谷胱甘肽（GSH）是肺上皮内液中抗氧化防御的潜在重要成分。囊性纤维化（CF）患者有慢性炎症，其中氧化应激可能是一个因素。为了验证CF患者GSH含量运输缺陷的假设，我们用高效液相色谱法测定了细胞内和细胞外的GSH。使用四种细胞系：CFT1细胞[带有缺陷的CF跨膜传导调节因子（CFTR）， Delta F508纯合子，两个克隆]和一个CFT1克隆转染正常CFTR （CFTR充满）或β -半乳糖苷酶。cftr缺乏培养的细胞根尖液中GSH含量比cftr补充培养的细胞低55% （P < 0.001）。相比之下，细胞内GSH含量在CFT1细胞和cftr细胞中相似。降解细胞外谷胱甘肽的γ -谷氨酰转肽酶活性不能解释顶端谷胱甘肽的差异。相反，cftr缺陷细胞的GSH外排低于cftr补充细胞。这些研究表明CF根尖液GSH含量的降低是由于GSH运输异常与CFTR缺陷相关。
Glutathione (GSH) is a potentially important component of antioxidant defense in the epithelial lung lining fluid. Cystic fibrosis (CF) patients have chronic inflammation in which oxidative stress can be a factor. To examine the hypothesis that the transport of GSH content was defective in CF patients, intracellular and extracellular GSH were measured by HPLC. Four cell lines were used: CFT1 cells [with defective CF transmembrane conductance regulator (CFTR), Delta F508 homozygous, two clones] and one of the CFT1 clones transfected with either normal CFTR (CFTR repleted) or beta-galactosidase. GSH content in the apical fluid was 55% lower in CFTR-deficient cultures than in CFTR-repleted cells (P < 0.001). In contrast, intracellular GSH content was similar in CFT1 cells and CFTR-repleted cells. gamma-Glutamyl transpeptidase activity, which degrades extracellular GSH, did not account for differences in apical GSH. Rather, GSH efflux of CFTR-deficient cells was lower than that of CFTR-repleted cells. These studies suggested that decreased GSH content in the apical fluid in CF resulted from abnormal GSH transport associated with a defective CFTR.