Age‐related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP–Trx2–ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: changes to Trx2 in the auditory cortex

• Published in: The FEBS journal Vol. 282; no. 14; pp. 2758 - 2774
• Main Authors: Sun, Hai‐Ying, Hu, Yu‐Juan, Zhao, Xue‐Yan, Zhong, Yi, Zeng, Ling‐Ling, Chen, Xu‐Bo, Yuan, Jie, Wu, Jing, Sun, Yu, Kong, Wen, Kong, Wei‐Jia
• Format: Journal Article
• Language: English
• Published: England Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies 01.07.2015; Blackwell Publishing Ltd
• Subjects: age‐related hearing loss; Aging; animal models; Animals; Antioxidants; Antioxidants - metabolism; apoptosis; Apoptosis - genetics; auditory cortex; Auditory Cortex - cytology; Auditory Cortex - metabolism; Auditory Cortex - physiology; Auditory Cortex - ultrastructure; Carrier Proteins - genetics; Carrier Proteins - metabolism; chronic exposure; cortex; Enzymes; galactose; Gene Expression Regulation; Hearing loss; homeostasis; Malondialdehyde - metabolism; MAP Kinase Kinase Kinase 5 - genetics; MAP Kinase Kinase Kinase 5 - metabolism; Mitochondria; Mitochondria - metabolism; oxidant stress; Oxidative Stress; pathogenesis; phenotype; rats; Rats, Sprague-Dawley; reactive oxygen species; signal transduction; speech; Superoxide Dismutase - metabolism; Thioredoxins - genetics; Thioredoxins - metabolism; thioredoxin 2; apoptosis; oxidant stress; thioredoxin 2; auditory cortex; age-related hearing loss
• ISSN: 1742-464X; 1742-4658; 1742-4658
• DOI: 10.1111/febs.13324

Age‐associated degeneration in the central auditory system, which is defined as central presbycusis, can impair sound localization and speech perception. Research has shown that oxidative stress plays a central role in the pathological process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin family, plays a key role in regulating the homeostasis of cellular reactive oxygen species and anti‐apoptosis. The purpose of this study was to explore the association between Trx2 and the phenotype of central presbycusis using a mimetic aging animal model induced by long‐term exposure to d‐galactose (d‐Gal). We also explored changes in thioredoxin‐interacting protein (TXNIP), apoptosis signal regulating kinase 1 (ASK1) and phosphorylated ASK1 (p‐ASK1) expression, as well as the Trx2–TXNIP/Trx2–ASK1 binding complex in the auditory cortex of mimetic aging rats. Our results demonstrate that, compared with control groups, the levels of Trx2 and Trx2–ASK1 binding complex were significantly reduced, whereas TXNIP, ASK1 p‐ASK1 expression, and Trx2–TXNIP binding complex were significantly increased in the auditory cortex of the mimetic aging groups. Our results indicated that changes in Trx2 and the TXNIP–Trx2–ASK1 signal pathway may participate in the pathogenesis of central presbycusis.