NADPH oxidase 2-dependent oxidative stress, mitochondrial damage and apoptosis in the ventral cochlear nucleus of d-galactose-induced aging rats. (12th February 2015)

• Record Type: Journal Article
• Authors: Du, Z.; Yang, Q.; Liu, L.; Li, S.; Zhao, J.; Hu, J.; Liu, C.; Qian, D.; Gao, C.
• Is Part Of: Neuroscience. Volume 286(2015)
• Page Start: 281
• Page End: 292
• Publication Date: 2015-02-12
• Subjects: 8-OHdG 8-hydroxy-2-deoxyguanosine -- CAS central auditory system -- CD common deletion -- cyt c cytochrome c -- DAPI 4′, 6-diamidino-2-phenylindole -- d-gal d-galactose -- MDA malondialdehyde -- MMP mitochondrial membrane potential -- mtDNA mitochondrial DNA -- NOXs NADPH oxidases -- NOX2 NADPH oxidase 2 -- PAS peripheral auditory system -- PBS Phosphate-buffered saline -- RE relative expression -- ROS reactive oxygen species -- TBS Tris-buffered saline -- TEM transmission electron microscopy -- T-SOD total superoxide dismutase -- TUNEL terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling -- VCN ventral cochlear nucleus; age-related hearing loss -- central auditory system (CAS) -- NADPH oxidase 2 (NOX2) -- oxidative damage -- mitochondrial DNA common deletion (mtDNA CD) -- apoptosis; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2014.11.061
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: d -Galactose increases NADPH oxidase 2 expression in the ventral cochlear nucleus. d -Galactose increases mitochondrial damage in the ventral cochlear nucleus. d -Galactose activates mitochondrial apoptotic pathway in the ventral cochlear nucleus. Abstract: 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 usingd -galactose (d -gal) and revealed that chronic injection ofd -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 thed -gal-induced aging rats. We found that the levels of H2 O2 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) ofd -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 ofd -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 byd -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 ind -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.