Senescence marker protein-30 protects mice lungs from oxidative stress, aging, and smoking
Senescence marker protein-30 protects mice lungs from oxidative stress, aging, and smoking
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DOI：
10.1164/rccm.200511-1816oc
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发表时间：
2006-09-01
影响因子：
24.7
通讯作者：
Ishigami, Alkihito
中科院分区：
文献类型：
--
作者：
Sato, Tadashi;Seyama, Kuniaki;Ishigami, Alkihito
原理：衰老标志蛋白-30 （SMP30）是一种多功能蛋白，可保护细胞功能免受年龄相关退化的影响。我们之前报道过SMP30基因敲除（SMP30Y/-）小鼠能够成为老年肺的新模型，具有与年龄相关的空域扩大和对有害刺激的易感性增强。目的：年龄和吸烟被认为是肺气肿发生的主要因素。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的影响。方法：观察野生型（SMP30Y/+）和野生型（SMP30Y/ -）小鼠肺组织中蛋白羰基的年龄相关性变化。两株菌株均暴露于香烟烟雾8周。测定肺组织病理学和形态学评价，肺组织中蛋白羰基和丙二醛含量，支气管肺泡灌洗液中总谷胱甘肽含量，肺细胞凋亡程度。测量结果及主要结果：SMP30Y/-小鼠肺中蛋白羰基随年龄增长呈增加趋势，显著高于年龄匹配的SMP30Y/+小鼠。香烟烟雾暴露在SMP30Y/-小鼠中产生明显的空域扩大（平均线性截距增加23.3%）和显著的实质破坏，而在SMP30Y/+小鼠中没有（5.4%）。暴露于香烟烟雾8周后，SMP30Y/-小鼠肺细胞的蛋白羰基、丙二醛、总谷胱甘肽和凋亡显著增加。结论：我们的研究结果表明SMP30可以保护小鼠肺部免受与衰老和吸烟相关的氧化应激。SMP30Y/-小鼠可能是研究与年龄相关的肺部疾病（包括香烟烟雾引起的肺气肿）的有用动物模型。
Rationale: 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.Objectives: 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.Methods: 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.Measurements and Main Results: 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.Conclusions: 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.