کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5854215 1130885 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
γ-Glutamyl transpeptidase null mice fail to develop tolerance to coumarin-induced Clara cell toxicity
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش تغذیه
پیش نمایش صفحه اول مقاله
γ-Glutamyl transpeptidase null mice fail to develop tolerance to coumarin-induced Clara cell toxicity
چکیده انگلیسی
Coumarin was used as a model Clara cell toxicant to test the hypothesis that tolerance to injury requires increased γ-glutamyl transpeptidase (GGT) activity. Wildtype (GGT+/+) and GGT-deficient (GGT−/−) mice on a C57BL/6/129SvEv hybrid background were dosed orally with corn oil (vehicle) or coumarin (200 mg/kg). In vehicle-treated mice, Clara cell secretory protein (CC10) expression was distributed throughout the bronchiolar epithelium. After one dose of coumarin, CC10 expression was dramatically reduced and the bronchiolar epithelium was devoid of Clara cells in GGT+/+ and GGT−/− mice. In wildtype mice, 9 doses of coumarin produced tolerance, characterized as a renewed bronchiolar epithelium with Clara cells expressing CC10 along with a 40% increase in total glutathione (GSH) and a 7-fold increase in GGT activity in the lung. In contrast, tolerance was not observed in GGT−/− mice. To assess whether changes in whole lung levels of GSH and GGT activity reflect Clara cell specific changes an enriched population of cells was isolated from female wildtype B6C3F1 mice made tolerant to coumarin. Compared to Clara cells from control mice, GSH and GGT activity increased 3- and 13-fold, respectively. Collectively, these data suggest Clara cell tolerance to coumarin toxicity requires increased GGT activity favoring enhanced GSH synthesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Food and Chemical Toxicology - Volume 48, Issue 6, June 2010, Pages 1612-1618
نویسندگان
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