Upregulation of thioredoxin contributes to inhibiting diabetic hearing impairment

Abstract

Aims: Hair cell reduction was related to diabetes-induced hearing loss. Oxidative stress, endoplasmic reticulum stress, and autophagy participate in this process. Thioredoxin (Trx) is a protein with many biological functions which can regulate them. In this study, aiming to clarify protective effect of Trx on diabetic hearing loss and to identify an early potential therapeutic target for diabetic hearing impairment in the future.

Methods: Trx transgenic (Tg) mice were used to establish a diabetic model by intraperitoneally injecting streptozotocin (STZ) and with/without SF or PX12 treatment. Succinate dehydrogenase (SDH) staining was used to evaluate the loss of hair cells. The relative expression of related proteins and genes was detected using western blotting and qRT-PCR.

Results: In vivo, loss of outer hair cells was observed. However, it can be delayed Trx overexpression. Moreover, the expression of PGC-1α, bcl-2 and LC3 was increased in Tg(+)-DM mice compared with Tg(-)-DM mice. The expression of ASK1, Txnip, GRP78, CHOP and p62 was decreased in Tg(+)-DM mice compared with Tg(-)-DM mice.

Conclusions: Upregulation of Trx protects diabetes-induced cochlear hair cells reduction. The underlying mechanisms were related to the regulation of ER stress through ASK1 and the mitochondrial pathway or autophagy via Txnip.

Keywords: Autophagy; Diabetes; Endoplasmic reticulum stress; Hearing impairment; Mitochondria; Thioredoxin.