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