Linked Life Data

11390189

Source:http://linkedlifedata.com/resource/pubmed/id/11390189

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2001-6-6
pubmed:abstractText
Though the cause of cystic fibrosis (CF) pathology is understood to be the mutation of the CFTR protein, it has been difficult to trace the exact mechanisms by which the pathology arises and progresses from the mutation. Recent research findings have noted that the CFTR channel is not only permeant to chloride anions, but other, larger organic anions, including reduced glutathione (GSH). This explains the longstanding finding of extracellular GSH deficit and dramatically reduced extracellular GSH:GSSG (glutathione disulfide) ratio found to be chronic and progressive in CF patients. Given the vital role of GSH as an antioxidant, a mucolytic, and a regulator of inflammation, immune response, and cell viability via its redox status in the human body, it is reasonable to hypothesize that this condition plays some role in the pathogenesis of CF. This hypothesis is advanced by comparing the literature on pathological phenomena associated with GSH deficiency to the literature documenting CF pathology, with striking similarities noted. Several puzzling hallmarks of CF pathology, including reduced exhaled NO, exaggerated inflammation with decreased immunocompetence, increased mucus viscoelasticity, and lack of appropriate apoptosis by infected epithelial cells, are better understood when abnormal GSH transport from epithelia (those without anion channels redundant to the CFTR at the apical surface) is added as an additional explanatory factor. Such epithelia should have normal levels of total glutathione (though perhaps with diminished GSH:GSSG ratio in the cytosol), but impaired GSH transport due to CFTR mutation should lead to progressive extracellular deficit of both total glutathione and GSH, and, hypothetically, GSH:GSSG ratio alteration or even total glutathione deficit in cells with redundant anion channels, such as leukocytes, lymphocytes, erythrocytes, and hepatocytes. Therapeutic implications, including alternative methods of GSH augmentation, are discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0891-5849
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1440-61
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed-meshheading:11390189-Antioxidants, pubmed-meshheading:11390189-Apoptosis, pubmed-meshheading:11390189-Biological Transport, pubmed-meshheading:11390189-Cystic Fibrosis, pubmed-meshheading:11390189-Cystic Fibrosis Transmembrane Conductance Regulator, pubmed-meshheading:11390189-Cytokines, pubmed-meshheading:11390189-Disease Susceptibility, pubmed-meshheading:11390189-Drug Administration Routes, pubmed-meshheading:11390189-Endopeptidases, pubmed-meshheading:11390189-Gene Expression Regulation, pubmed-meshheading:11390189-Glutathione, pubmed-meshheading:11390189-Humans, pubmed-meshheading:11390189-Immune System, pubmed-meshheading:11390189-Infection, pubmed-meshheading:11390189-Lung, pubmed-meshheading:11390189-Models, Biological, pubmed-meshheading:11390189-Mucus, pubmed-meshheading:11390189-NF-kappa B, pubmed-meshheading:11390189-Nitric Oxide, pubmed-meshheading:11390189-Oxidation-Reduction, pubmed-meshheading:11390189-Oxidative Stress, pubmed-meshheading:11390189-Protease Inhibitors, pubmed-meshheading:11390189-Tumor Necrosis Factor-alpha
pubmed:year
2001
pubmed:articleTitle
Rethinking cystic fibrosis pathology: the critical role of abnormal reduced glutathione (GSH) transport caused by CFTR mutation.
pubmed:affiliation
Brigham Young University, Provo, UT 84602, USA. valerie_hudson@byu.edu
pubmed:publicationType
Journal Article, Review