scholarly journals Cystic Fibrosis Transmembrane Conductance Regulator Controls Lung Proteasomal Degradation and Nuclear Factor-κB Activity in Conditions of Oxidative Stress

2008 ◽  
Vol 172 (5) ◽  
pp. 1184-1194 ◽  
Author(s):  
Emilie Boncoeur ◽  
Telma Roque ◽  
Elise Bonvin ◽  
Vinciane Saint-Criq ◽  
Monique Bonora ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Proteasomal Degradation ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane

Constitutive Activation of Nuclear Factor κB Contributes to Cystic Fibrosis Transmembrane Conductance Regulator Expression and Promotes Human Cervical Cancer Progression and Poor Prognosis

2013 ◽  
Vol 23 (5) ◽  
pp. 906-915 ◽  
Author(s):  
Zhao Wu ◽  
Xue Peng ◽  
Jinke Li ◽  
Yi Zhang ◽  
Lina Hu
Keyword(s):  
Cystic Fibrosis ◽  
Cervical Cancer ◽  
Multivariate Analysis ◽  
Poor Prognosis ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Transmembrane Conductance Regulator ◽  
Cervical Tissue ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane

ObjectiveCystic fibrosis transmembrane conductance regulator (CFTR) and nuclear factor κB (NF-κB) have been known to play important roles in the development and progression of many types of cancer including cervical cancer. The study aimed to verify the relevance and significance of CFTR and NF-κB expressions in cervical cancer tissues and cell lines.MethodsThe expressions of CFTR and NF-κB p65 were analyzed respectively by immunohistochemistry in total of 135 cervical tissue samples. The correlation to clinicopathologic characteristics and prognostic value was evaluated. The coexpression of CFTR and NF-κB was detected in cervical cancer cell lines. Nuclear factor κB signaling was inhibited by siRNA for NF-κB p65 and activated by stimulation of cells with interleukin β or tumor necrosis factor α.ResultsWe found both the membrane expression of CFTR and nuclear translocation of NF-κB p65 were progressively increased from normal cervical tissue, cervical intraepithelial neoplasm, to cervical cancer (overallR2= 0.74,P< 0.001). Cystic fibrosis transmembrane conductance regulator expression and NF-κB activation were also positively associated with stage, histological grade, lymph node metastasis, and invasive interstitial depth. Multivariate analysis showed that coexpression of CFTR and NF-κB was an independent prognostic factor for survival (relative risk, 5.16;P= 0.003). Dual-immunofluorescence analysis showed CFTR and NF-κB were coexpressed in cervical cancer. Studies in vitro revealed that the expression levels of CFTR mRNA and protein were positively related to NF-κB activation.ConclusionsCystic fibrosis transmembrane conductance regulator and NF-κB were coexpressed in cervical cancer, and the activation of NF-κB mediated the expression of CFTR. Multivariate analysis revealed that coexpression of CFTR and NF-κB was associated with poor prognosis in patients with cervical cancer.

Glutathione permeability of CFTR

1998 ◽  
Vol 275 (1) ◽  
pp. C323-C326 ◽  
Author(s):  
Paul Linsdell ◽  
John W. Hanrahan
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Ion Channel ◽  
Airway Epithelial Cells ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Transmembrane Conductance ◽  
High Concentrations ◽  
Cystic Fibrosis Transmembrane ◽  
Glutathione Transport

The cystic fibrosis transmembrane conductance regulator (CFTR) forms an ion channel that is permeable both to Cl− and to larger organic anions. Here we show, using macroscopic current recording from excised membrane patches, that the anionic antioxidant tripeptide glutathione is permeant in the CFTR channel. This permeability may account for the high concentrations of glutathione that have been measured in the surface fluid that coats airway epithelial cells. Furthermore, loss of this pathway for glutathione transport may contribute to the reduced levels of glutathione observed in airway surface fluid of cystic fibrosis patients, which has been suggested to contribute to the oxidative stress observed in the lung in cystic fibrosis. We suggest that release of glutathione into airway surface fluid may be a novel function of CFTR.

scholarly journals Traffic-independent function of the Sar1p/COPII machinery in proteasomal sorting of the cystic fibrosis transmembrane conductance regulator

2003 ◽  
Vol 160 (2) ◽  
pp. 157-163 ◽  
Author(s):  
Lianwu Fu ◽  
Elizabeth Sztul
Keyword(s):  
Cystic Fibrosis ◽  
Proteasomal Degradation ◽  
Degradation Pathway ◽  
Restrictive Temperature ◽  
Transmembrane Conductance Regulator ◽  
Nucleotide Exchange ◽  
Transmembrane Conductance ◽  
Yeast Saccharomyces Cerevisiae ◽  
Nucleotide Exchange Factor ◽  
Cystic Fibrosis Transmembrane

Newly synthesized proteins that do not fold correctly in the ER are targeted for ER-associated protein degradation (ERAD) through distinct sorting mechanisms; soluble ERAD substrates require ER-Golgi transport and retrieval for degradation, whereas transmembrane ERAD substrates are retained in the ER. Retained transmembrane proteins are often sequestered into specialized ER subdomains, but the relevance of such sequestration to proteasomal degradation has not been explored. We used the yeast Saccharomyces cerevisiae and a model ERAD substrate, the cystic fibrosis transmembrane conductance regulator (CFTR), to explore whether CFTR is sequestered before degradation, to identify the molecular machinery regulating sequestration, and to analyze the relationship between sequestration and degradation. We report that CFTR is sequestered into ER subdomains containing the chaperone Kar2p, and that sequestration and CFTR degradation are disrupted in sec12ts strain (mutant in guanine-nucleotide exchange factor for Sar1p), sec13ts strain (mutant in the Sec13p component of COPII), and sec23ts strain (mutant in the Sec23p component of COPII) grown at restrictive temperature. The function of the Sar1p/COPII machinery in CFTR sequestration and degradation is independent of its role in ER-Golgi traffic. We propose that Sar1p/COPII-mediated sorting of CFTR into ER subdomains is essential for its entry into the proteasomal degradation pathway. These findings reveal a new aspect of the degradative mechanism, and suggest functional crosstalk between the secretory and the degradative pathways.

scholarly journals An Intriguing Involvement of Mitochondria in Cystic Fibrosis

2019 ◽  
Vol 8 (11) ◽  
pp. 1890 ◽  
Author(s):  
Favia ◽  
de Bari ◽  
Bobba ◽  
Atlante
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Causative Factor ◽  
Transmembrane Conductance Regulator ◽  
Many Body ◽  
Transmembrane Conductance ◽  
Leading Role ◽  
Elevated Glucose ◽  
Cftr Protein ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) occurs when the cystic fibrosis transmembrane conductance regulator (CFTR) protein is not synthetized and folded correctly. The CFTR protein helps to maintain the balance of salt and water on many body surfaces, such as the lung surface. When the protein is not working correctly, chloride becomes trapped in cells, then water cannot hydrate the cellular surface and the mucus covering the cells becomes thick and sticky. Furthermore, a defective CFTR appears to produce a redox imbalance in epithelial cells and extracellular fluids and to cause an abnormal generation of reactive oxygen species: as a consequence, oxidative stress has been implicated as a causative factor in the aetiology of the process. Moreover, massive evidences show that defective CFTR gives rise to extracellular GSH level decrease and elevated glucose concentrations in airway surface liquid (ASL), thus encouraging lung infection by pathogens in the CF advancement. Recent research in progress aims to rediscover a possible role of mitochondria in CF. Here the latest new and recent studies on mitochondrial bioenergetics are collected. Surprisingly, they have enabled us to ascertain that mitochondria have a leading role in opposing the high ASL glucose level as well as oxidative stress in CF.

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