Thioredoxin-1 protects against hyperoxia-induced apoptosis in cells of the alveolar walls |
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Authors: | Yamada Tadaaki Iwasaki Yoshinobu Nagata Kazuhiro Fushiki Shinji Nakamura Hajime Marunaka Yoshinori Yodoi Junji |
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Affiliation: | Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. tadaaki-y@muc.biglobe.ne.jp |
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Abstract: | BACKGROUND: The 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. METHODS: Mice were exposed to 98% O(2) to produce a model of hyperoxia-induced lung injury. Using transgenic mice overexpressing human TRX-1 (hTRX-1), we assessed lung structure (n=4 per group), immunohistochemical staining for 8-hydroxy-deoxyguanosine (n=4 per group), TUNEL staining (n=5 per group), cytokine (n=5 per group) of IL-1beta and IL-6, and protein (n=6 per group) and m-RNA levels (n=4 per group) (or both) of cytochrome c, Bcl-2, Bax, p21, and p53 in the lungs. RESULTS: After 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-1beta. CONCLUSIONS: These 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. |
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Keywords: | Thioredoxin-1 Apoptosis Hyperoxia Acute lung injury Bcl-2 Cytochrome c IL-6 |
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