文章基本信息

标题：SRT1720, a SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice
本地全文：下载
作者：Shingo Imanishi ; Ryuji Hayashi ; Tomomi Ichikawa 等
期刊名称：Food and Nutrition Sciences
印刷版ISSN：2157-944X
电子版ISSN：2157-9458
出版年度：2012
卷号：3
期号：2
页码：157-163
DOI：10.4236/fns.2012.32024
出版社：Scientific Research Publishing
摘要：Diagnosis and management of interstitial lung diseases (ILDs), caused by lung epithelial injury followed by apoptosis, are often challenging. It has been controversial whether the SIRT1 protein, a principal modulator of longevity due to caloric restriction, ameliorates or aggravates ILD in animal models. Here we examined the effect of SRT1720, a syn- thetic activator of SIRT1, on bleomycin-induced lung injury in a mouse model and apoptosis in cultured epithelial cells. Oral intubation of SRT1720 over a period of 15 days caused body weight loss and a high mortality rate among bleomy- cin-treated mice. Histological examinations showed that the SRT1720 load increased fibrosis in the bleomycin-treated lung. An analysis of bronchoalveolar lavage fluid revealed remarkably increased numbers of inflammatory cells in the SRT1720-treated group. Moreover, the apoptosis of A549 lung cancer cells, caused by X-ray irradiation and an anti-Fas activating antibody, was promoted by SRT1720. These results indicate that SRT1720 not only aggravates bleomy- cin-induced ILD, but stimulates the apoptosis of physically and biologically stimulated A549 cells. While SIRT1 acti- vators are considered promising for the treatment of conditions such as diabetes mellitus, fatty liver, and chronic ob- structive pulmonary diseases, an excess of food containing SIRT1 activators may be harmful depending on the disease state, especially in the case of acute inflammation.
关键词：Interstitial Lung Diseases (ILDs); Lung Injury; SIRT1; Bleomycin; X-Ray Irradiation; Oxidative Stress