کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2567879 | 1561094 | 2007 | 10 صفحه PDF | دانلود رایگان |
BackgroundThe mechanisms of hyperoxia-induced lung injury remain poorly defined. Thioredoxin-1 (TRX-1) is a small ubiquitous protein that acts as an important radical scavenger. We investigated the effect of TRX-1 on apoptosis in hyperoxia-induced lung injury.MethodsMice were exposed to 98% O2 to produce a model of hyperoxia-induced lung injury. Using transgenic mice overexpressing human TRX-1 (hTRX-1), we assessed lung structure (n=4n=4 per group), immunohistochemical staining for 8-hydroxy-deoxyguanosine (n=4n=4 per group), TUNEL staining (n=5n=5 per group), cytokine (n=5n=5 per group) of IL-1β and IL-6, and protein (n=6n=6 per group) and m-RNA levels (n=4n=4 per group) (or both) of cytochrome c, Bcl-2, Bax, p21, and p53 in the lungs.ResultsAfter exposure to hyperoxia, hTRX-1 transgenic mice had significantly decreased alveolar damage. The apoptotic index was significantly lower in hTRX-1 transgenic mice than in wild-type (WT) mice after exposure to hyperoxia. Protein expression of cytochrome c in the lung was significantly lower in hTRX-1 transgenic mice than in WT mice after exposure to hyperoxia. Protein expression and m-RNA levels of Bcl-2 in the lung were significantly higher in hTRX-1 transgenic mice than in WT mice after exposure to hyperoxia. TRX-1 had no effect on the protein and m-RNA levels of Bax and p21. The protein and m-RNA levels of p53 was unaffected by hyperoxia in hTRX-1 transgenic mice. The cytokine level of IL-6 was significantly higher in hTRX-1 transgenic mice than in WT mice after exposure to hyperoxia. TRX-1 had no effect on cytokine level of IL-1β.ConclusionsThese findings suggest that overexpression of hTRX-1 protects against hyperoxia-induced apoptosis in cells of the alveolar walls. The up-regulating Bcl-2 protein is considered to be one of antiapoptotic effects of TRX-1 in hyperoxia-induced lung injury.
Journal: Pulmonary Pharmacology & Therapeutics - Volume 20, Issue 6, December 2007, Pages 650–659