NADPH Oxidase-dependent Oxidative Stress and Mitochondrial Damage in Hippocampus of D-galactose-induced Aging Rats  

作　　者：杜政德 胡钰娟 杨阳 孙宇 张甦琳 周涛 曾玲玲 张文娟 黄翔 孔维佳 张红莲 

机构地区：[1]Department of Otorhinolaryngology [2]Department of Otorhinolaryngology,Shenzhen Sixth People's Hospital(Nanshan Hospital),Huazhong University of Science and Technology [3]Department of Public Health,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2012年第4期466-472,共7页华中科技大学学报（医学英德文版）

基　　金：supported by grants from the Natural Science Foundation of Hubei province (No. 2010CDB08005);the National Natural Science Foundation of China (No. 30730094 and81000409);Special Funds for State Key Development Program for Basic Research of China (973 Program) (No.2011CB504504)

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.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.

关 键 词：D-GALACTOSE common deletion oxidative stress NADPH oxidase uncoupling protein 2 

分 类 号：R363[医药卫生—病理学]