Flowchart: Preparation: Cftr
 

 


                                                      

Text Box:  Exogenous
 Oxidant stress
                                        

                                                                       

 

                                                                                                                                                                                                                     

                                                                                                

Text Box:   Aldh2Text Box: Cftr                                                                                           

                                              

 

 

 

Oxidant stress suppresses CFTR expression.

Cantin AM, Bilodeau G, Ouellet C, Liao J, Hanrahan JW.

Pulmonary Division, University of Sherbrooke, Sherbrooke, Quebec, Canada.

Epithelial mucous membranes are repeatedly exposed to oxidants and xenobiotics. Cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in glutathione trans-epithelial flux, and in defining the hydration and viscoelasticity of protective mucus. We thus hypothesized that CFTR expression and function may be modulated by oxidant stress. A sub-lethal oxidant stress (tert-butylhydroquinone, tBHQ) in CFTR expressing epithelial cells (T84) induced a significant increase in cellular glutathione that was associated with an increase in the expression of the gene encoding the heavy subunit of the rate-limiting enzyme for glutathione synthesis, gamma-glutamylcysteine synthetase (gammaGCShs). CFTR gene expression was markedly decreased according to a time-course that mirrored the changes in gammaGCShs. Western blot analysis confirmed that the decrease in cftr gene expression was associated with a decrease in CFTR protein. cAMP-dependent iodide efflux was also decreased by the oxidant stress. Nuclear run-on assays indicated that the oxidant stress had no effect on CFTR gene transcription but the mRNA stability in the oxidant-stressed cells was markedly reduced. Furthermore, tBHQ increased gammaGCShs mRNA while decreasing CFTR mRNA in Calu-3 cells, and taurine chloramine induced similar effects in T84 cells. We conclude that suppression of CFTR expression may represent an adaptive response of mucosal epithelium to an exogenous oxidant stress.

PMID: 16162662 [PubMed - as supplied by publisher]

 

 

Certain background factors exhibit an association with an increased risk for pancreatic calcification among Japanese male alcoholics.

Nakamura Y, Ohmori T, Higuchi S, Maruyama K.

Department of Clinical Research, National Hospital Organization Kurihama Alcoholism Center, Kanagawa, Japan. yuji-nakamura@mtg.biglobe.ne.jp

OBJECTIVE: This was a cross-sectional study conducted from April 2003 through March 2004 to investigate the background factors related to pancreatic calcification (PC) in male Japanese alcoholics. METHODS AND RESULTS: Helical computed tomography examination revealed PC in 44 of 263 alcoholics, and this group was further divisible into 3 subgroups: "scant" (n = 24), "moderate" (n = 6), and "extensive" PC subgroups (n = 14). The extensive subgroup was associated with larger daily ethanol consumption (P = 0.05) and high-alcohol beverages, such as whisky (P = 0.02). The moderate subgroup was associated with a longer duration of habitual drinking (P = 0.04), whereas the scant PC group was associated with never having smoked (P = 0.05) and with low-alcohol beverages, such as beer (P = 0.09). None of the 40 subjects with inactive mitochondrial aldehyde dehydrogenase (ALDH2*2 allele) exhibited PC (P = 0.004). Heterozygous alcohol dehydrogenase 2 genotype (ADH2*1/2*2) exhibited an association with the scant subgroup (P = 0.02). The TG12 repeats in the cystic fibrosis transmembrane conductance regulator (CFTR) gene tended to have a weak association with PC. CONCLUSION: Drinking behavior, smoking status, and genetic backgrounds are associated with PC and are likely to increase the risk for alcoholic chronic pancreatitis.