NADPH OXIDASE 2-DEPENDENT OXIDATIVE STRESS, MITOCHONDRIAL DAMAGE AND APOPTOSIS IN THE VENTRAL COCHLEAR NUCLEUS OF D-GALACTOSE-INDUCED AGING RATS

被引：43

作者：

Du, Z. ^{[1
]}

Yang, Q. ^{[1
]}

Liu, L. ^{[2
]}

Li, S. ^{[1
]}

Zhao, J. ^{[1
]}

Hu, J. ^{[1
]}

Liu, C. ^{[1
]}

Qian, D. ^{[1
]}

Gao, C. ^{[1
]}

机构：

[1] Guangdong Med Coll, Dept Otorhinolaryngol, Nanshan Affiliated Hosp, Shenzhen 518052, Peoples R China

[2] Guangxi Med Univ, Coll Pharm, Nanning 530021, Peoples R China

来源：

NEUROSCIENCE | 2015年 / 286卷

关键词：

age-related hearing loss; central auditory system (CAS); NADPH oxidase 2 (NOX2); oxidative damage; mitochondrial DNA common deletion (mtDNA CD); apoptosis; INNER-EAR; FUNCTIONAL-CHANGES; QUANTITATIVE PCR; COMMON DELETION; DNA MUTATIONS; HEARING-LOSS; NOX FAMILY; DEFICIENCY; EXPRESSION; CANCER;

D O I：

10.1016/j.neuroscience.2014.11.061

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Aging has been associated with oxidative stress and the accumulation of mitochondrial DNA (mtDNA) mutation. The previous study has established a mimetic rat model of aging using D-galactose (D-gal) and revealed that chronic injection of D-gal can increase NADPH oxidase (NOX)-dependent oxidative stress, mitochondrial damage and apoptosis in the peripheral auditory system. However, the effects of NOXs in the central auditory system (CAS) were still obscure. The current study was designed to investigate potential causative mechanisms of central presbycusis by using the D-gal-induced aging rats. We found that the levels of H2O2 and the expression of NADPH oxidase 2 (NOX2) and its corresponding subunits P22(phox), P47(phox) and P67(phox) were greatly increased in the ventral cochlear nucleus (VCN) of D-gal-treated rats as compared with controls. And, the levels of a typical biomarker of oxidative stress, 8-hydroxy-2-deoxyguanosine (8-OHdG), and the accumulation of mtDNA common deletion (CD) were also increased in the VCN of D-gal-treated rats as compared with controls. Moreover, the damage of mitochondrial ultrastructure, a decline in ATP levels, the loss of mitochondrial membrane potential (MMP), an increase in the amount of cytochrome c (cyt c) translocated to the cytoplasm and caspase-3 activation were observed in the VCN induced by D-gal. In addition, we also found that the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling (TUNEL)-positive cells in the VCN were increased in D-gal-treated rats. Taken together, these findings suggest that NOX2-dependent oxidative stress may contribute to mitochondrial damage and activate a caspase-3-dependent apoptosis pathway in the CAS during aging. This study also provides new insights into the development of presbycusis. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：281 / 292

页数：12

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