NADPH oxidase-dependent oxidative stress and mitochondrial damage in hippocampus of D-galactose-induced aging rats

被引:21
作者
Du, Zhengde [1 ,3 ]
Hu, Yujuan [1 ]
Yang, Yang [1 ]
Sun, Yu [1 ]
Zhang, Sulin [1 ]
Zhou, Tao [1 ]
Zeng, Lingling [1 ]
Zhang, Wenjuan [1 ]
Huang, Xiang [1 ]
Kong, Weijia [1 ]
Zhang, Honglian [2 ]
机构
[1] Huazhong Univ Sci & Technol, Dept Otorhinolaryngol, Tongji Med Coll, Union Hosp, Wuhan 430022, Peoples R China
[2] Huazhong Univ Sci & Technol, Dept Publ Hlth, Tongji Med Coll, Union Hosp, Wuhan 430022, Peoples R China
[3] Huazhong Univ Sci & Technol, Dept Otorhinolaryngol, Shenzhen Peoples Hosp 6, Nanshan Hosp, Shenzhen 518052, Peoples R China
基金
中国国家自然科学基金;
关键词
D-galactose; common deletion; oxidative stress; NADPH oxidase; uncoupling protein 2; DNA DELETIONS; ENERGY-METABOLISM; BP DELETION; MEMORY LOSS; NEURO DEGENERATION; COMMON DELETION; SKELETAL-MUSCLE; INNER-EAR; MICE; BRAIN;
D O I
10.1007/s11596-012-0081-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Mitochondrial DNA (mtDNA) common deletion (CD) plays a significant role in aging and age-related diseases. In this study, we used D-galactose (D-gal) to generate an animal model of aging and the involvement and causative mechanisms of mitochondrial damage in such a model were investigated. Twenty 5-week-old male Sprague-Dawley rats were randomly divided into two groups: D-gal group (n=10) and control group (n=10). The quantity of the mtDNA CD in the hippocampus was determined using a TaqMan real-time PCR assay. Transmission electron microscopy was used to observe the mitochondrial ultrastructure in the hippocampus. Western blot was used to detect the protein levels of NADPH oxidase (NOX) and uncoupling protein 2 (UCP2). We found that the level of mtDNA CD was significantly higher in the hippocampus of D-gal-induced aging rats than in control rats. In comparison with the control group, the mitochondrial ultrastructure in the hippocampus of D-gal-treated rats was damaged, and the protein levels of NOX and UCP2 were significantly increased in the hippocampus of D-gal-induced aging rats. This study demonstrated that the levels of mtDNA CD and NOX protein expression were significantly increased in the hippocampus of D-gal-induced aging rats. These findings indicate that NOX-dependent reactive oxygen species generation may contribute to D-gal-induced mitochondrial damage.
引用
收藏
页码:466 / 472
页数:7
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