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S-Nitrosothiols increases cystic fibrosis transmembrane regulator expression and maturation in the cell surface.

Abstract：

:S-nitrosothiols (SNOs) are endogenous signaling molecules with a broad spectrum of beneficial airway effects. SNOs are normally present in the airway, but levels tend to be low in cystic fibrosis (CF) patients. We and others have demonstrated that S-nitrosoglutathione (GSNO) increases the expression, maturation, and function of wild-type and mutant F508del cystic fibrosis transmembrane conductance regulator (CFTR) in human bronchial airway epithelial (HBAE) cells. We hypothesized that membrane permeable SNOs, such as S-nitrosoglutathione diethyl ester (GNODE) and S-nitroso-N-acetyl cysteine (SNOAC) may be more efficient in increasing the maturation of CFTR. HBAE cells expressing F508del CFTR were exposed to GNODE and SNOAC. The effects of these SNOs on the expression and maturation of F508del CFTR were determined by cell surface biotinylation and Western blot analysis. We also found for the first time that GNODE and SNOAC were effective at increasing CFTR maturation at the cell surface. Furthermore, we found that cells maintained at low temperature increased cell surface stability of F508del CFTR whereas the combination of low temperature and SNO treatment significantly extended the half-life of CFTR. Finally, we showed that SNO decreased the internalization rate of F508del CFTR in HBAE cells. We anticipate identifying the novel mechanisms, optimal SNOs, and lowest effective doses which could benefit cystic fibrosis patients.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Zaman K,Bennett D,Fraser-Butler M,Greenberg Z,Getsy P,Sattar A,Smith L,Corey D,Sun F,Hunt J,Lewis SJ,Gaston B

doi

10.1016/j.bbrc.2013.12.130

subject

Has Abstract

pub_date

2014-01-24 00:00:00

pages

1257-62

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(13)02201-8

journal_volume

443

pub_type

杂志文章

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