Gao L, Kim K J, Yankaskas J R, Forman H J
Department of Molecular Pharmacology and Toxicology, Will Rogers Institute Pulmonary Research Center, University of Southern California, Los Angeles, California 90033, USA.
Am J Physiol. 1999 Jul;277(1):L113-8. doi: 10.1152/ajplung.1999.277.1.L113.
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), DeltaF508 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.
谷胱甘肽（GSH）是肺上皮衬液中抗氧化防御的潜在重要组成部分。囊性纤维化（CF）患者存在慢性炎症，氧化应激可能是其中一个因素。为了检验CF患者中GSH含量转运存在缺陷这一假说，通过高效液相色谱法（HPLC）测量细胞内和细胞外的GSH。使用了四种细胞系：CFT1细胞[囊性纤维化跨膜传导调节因子（CFTR）有缺陷，ΔF508纯合，两个克隆]以及用正常CFTR（CFTR补充）或β-半乳糖苷酶转染的CFT1克隆之一。CFTR缺陷培养物中顶端液中的GSH含量比CFTR补充细胞中的低55%（P < 0.001）。相反，CFT1细胞和CFTR补充细胞中的细胞内GSH含量相似。降解细胞外GSH的γ-谷氨酰转肽酶活性并不能解释顶端GSH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患者顶端液中GSH含量降低是由于与缺陷CFTR相关的GSH转运异常所致。
