Sato Tadashi, Seyama Kuniaki, Sato Yasunori, Mori Hiroaki, Souma Sanae, Akiyoshi Taeko, Kodama Yuzo, Mori Takanori, Goto Sataro, Takahashi Kazuhisa, Fukuchi Yoshinosuke, Maruyama Naoki, Ishigami Akihito
Department of Respiratory Medicine, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
Am J Respir Crit Care Med. 2006 Sep 1;174(5):530-7. doi: 10.1164/rccm.200511-1816OC. Epub 2006 May 25.
Senescence marker protein-30 (SMP30) is a multifunctional protein providing protection to cellular functions from age-associated deterioration. We previously reported that SMP30 knockout (SMP30Y/-) mice are capable of being novel models for senile lung with age-related airspace enlargement and enhanced susceptibility to harmful stimuli.
Aging and smoking are considered as major contributing factors for the development of pulmonary emphysema. We evaluated whether SMP30Y/- mice are susceptible to oxidative stress associated with aging and smoking.
Age-related changes of protein carbonyls in lung tissues from the wild-type (SMP30Y/+) and SMP30Y/- mice were evaluated. Both strains were exposed to cigarette smoke for 8 wk. Histopathologic and morphologic evaluations of the lungs, protein carbonyls and malondialdehyde in the lung tissues, total glutathione content in the bronchoalveolar lavage fluid, and degree of apoptosis of lung cells were determined.
In the lungs of SMP30Y/- mice, protein carbonyls tended to increase with aging and were significantly higher than the age-matched SMP30Y/+ mice. Cigarette smoke exposure generated marked airspace enlargement (23.3% increase of the mean linear intercepts) with significant parenchymal destruction in the SMP30Y/- mice but not in the SMP30Y/+ mice (5.4%). The protein carbonyls, malondialdehyde, total glutathione, and apoptosis of lung cells were significantly increased after 8-wk exposure to cigarette smoke in the SMP30Y/- mice.
Our results suggest that SMP30 protects mice lungs from oxidative stress associated with aging and smoking. The SMP30Y/- mice could be useful animal models for investigating age-related lung diseases, including cigarette smoke-induced pulmonary emphysema.
衰老标记蛋白-30（SMP30）是一种多功能蛋白，可保护细胞功能免受与年龄相关的衰退影响。我们之前报道过，SMP30基因敲除（SMP30Y/-）小鼠能够成为老年肺的新型模型，其具有与年龄相关的气腔扩大以及对有害刺激的易感性增加。
衰老和吸烟被认为是肺气肿发展的主要促成因素。我们评估了SMP30Y/-小鼠是否易受与衰老和吸烟相关的氧化应激影响。
评估野生型（SMP30Y/+）和SMP30Y/-小鼠肺组织中蛋白质羰基的年龄相关变化。两种品系的小鼠都暴露于香烟烟雾中8周。测定肺组织的组织病理学和形态学评估、肺组织中的蛋白质羰基和丙二醛、支气管肺泡灌洗液中的总谷胱甘肽含量以及肺细胞的凋亡程度。
在SMP30Y/-小鼠的肺中，蛋白质羰基倾向于随着年龄增长而增加，并且显著高于年龄匹配的SMP30Y/+小鼠。暴露于香烟烟雾导致SMP30Y/-小鼠出现明显的气腔扩大（平均线性截距增加23.3%）和显著的实质破坏，但SMP30Y/+小鼠中未出现（增加5.4%）。在SMP30Y/-小鼠中，暴露于香烟烟雾8周后，肺细胞的蛋白质羰基、丙二醛、总谷胱甘肽和凋亡显著增加。
我们的结果表明，SMP30可保护小鼠肺部免受与衰老和吸烟相关的氧化应激影响。SMP30Y/-小鼠可能是用于研究包括香烟烟雾诱导的肺气肿在内的与年龄相关的肺部疾病的有用动物模型。
