Upregulation of thioredoxin contributes to inhibiting diabetic hearing impairment

Ren, Xiang; Lv, Jinjuan; Fu, Yuzhen; Zhang, Na; Zhang, Chenghong; Dong, Zhenghao; Chudhary, Maryam; Zhong, Shiwen; Kong, Li; Kong, Hui

doi:10.1016/j.diabres.2021.109025

Cited by 8 publications

(3 citation statements)

References 39 publications

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“…Boosting lysosomal cathepsin D activity not only enhanced SNCA clearance in human and murine neurons as well as tissue, but also restored endo-lysosome and autophagy function [40]. The expressions of PINK1, Parkin and cathepsin D were related with Trx-1 expression in diabetic diseases and AD [42][43][44]. The decreased expression of cathepsin D by MPTP was restored in Trx-1 overexpressing mice and further decreased in Trx-1 knockdown mice (Fig.…”

Section: Discussionmentioning

confidence: 84%

Thioredoxin-1 decreases alpha-synuclein induced by MPTP through promoting autophagy-lysosome pathway

Bai

et al. 2023

Preprint

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Parkinson’s disease (PD) is characterized by Lewy body. Alpha-synuclein (α-syn) is a major component of Lewy body. Autophagy eliminates damaged organelles and abnormal aggregated proteins. Thioredoxin-1 (Trx-1) is a redox regulating protein and plays roles in protecting neurons against neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the relationship between Trx-1 and α-syn in PD is still unknown. The movement disorder and dopaminergic neurotoxicity in MPTP PD mice were improved by Trx-1 overexpression, whereas were aggravated by Trx-1 knockdown in the substantia nigra pars compacta (SNpc) in mice. α-syn was increased in MPTP PD mice, which was inhibited by Trx-1 overexpression, whereas was exacerbated in Trx-1 knockdown mice. The autophagosomes were increased by MPTP, which were recovered in Trx-1 overexpressing mice, while were further increased in Trx-1 knockdown in the SNpc in mice under electron microscope. The expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced putative kinase 1 (PINK1), Parkin, LC3 II and p62 were induced by MPTP, which were blocked in Trx-1 overexpressing mice, which were further increased in Trx-1 knockdown mice. Cathepsin D was decreased by MPTP, which was restored in Trx-1 overexpressing mice, while was further decreased in Trx-1 knockdown mice. The mRFP-GFP-LC3 green fluorescent dots were increased by 1-methyl-4-phenylpyridinium (MPP+) and more green fluorescent dots in Trx-1 siRNA transfection in PC 12 cells, but mRFP-GFP-LC3 red fluorescent dots were increased in Trx-1 overexpressing cells. These results indicate that Trx-1 may eliminate α-syn in PD mice through potentiating autophagy-lysosome pathway.

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Section: Discussionmentioning

confidence: 84%

Thioredoxin-1 decreases alpha-synuclein induced by MPTP through promoting autophagy-lysosome pathway

Bai

et al. 2023

Preprint

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“…A study by Ren et al identified the protective effect of Thioredoxin (Trx) on DM-induced SNHL and to identify an early potential therapeutic target for diabetic hearing impairment in the future [ 60 ]. Thioredoxin (Trx) is a small redox protein present in tissues which contains dithiol-disulfide active site, which functions to regulate oxidative stress [ 61 ], endoplasmic reticulum stress [ 62 ], and autophagy in biological processes [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

“…Ren et al demonstrated that elevating Trx levels with sulforaphane reduces DM-related cochlear hair cell damage [ 60 ]. Trx, known for its role in reducing apoptosis and supporting cell metabolism [ 71 ]., helps mitigate cochlear degeneration in DM by influencing mitochondrial function and reducing ER stress and autophagy.…”

Section: Discussionmentioning

confidence: 99%

Diabetes mellitus, hearing loss, and therapeutic interventions: A systematic review of insights from preclinical animal models

Mittal,

Keith,

Lacey

et al. 2024

PLoS ONE

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Objectives The aim of this systematic review article is to evaluate the relationship between diabetes mellitus (DM) and sensorineural hearing loss (SNHL) utilizing preclinical animal models. The review focused on studies assessing SNHL in diabetic animal models, elucidating the mechanisms of DM-associated SNHL, and exploring the response of diabetic animal models to noise overexposure. We also discussed studies investigating the efficacy of potential therapeutic strategies for amelioration of DM-associated SNHL in the animal models. Methods A protocol of this systematic review was designed a priori and was registered in the PROSPERO database (registration number: CRD42023439961). We conducted a comprehensive search on PubMed, Science Direct, Web of Science, Scopus, and EMBASE databases. A minimum of three reviewers independently screened, selected, and extracted data. The risk of bias assessment of eligible studies was conducted using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool. Results Following the screening of 238 studies, twelve original articles were included in this systematic review. The studies revealed that hyperglycemia significantly affects auditory function, with various pathological mechanisms contributing to DM-induced hearing impairment, including cochlear synaptopathy, microangiopathy, neuropathy, oxidative stress, mitochondrial abnormalities, and apoptosis-mediated cell death. Emerging interventions, such as Asiaticoside, Trigonelline, Chlorogenic acid, and Huotanquyu granules, demonstrated efficacy in providing otoprotection for preserving cochlear hair cells and hearing function. Conclusions Our systematic review delves into the intricate relationship between DM and hearing impairment in animal models. Future research should focus on targeted therapies to enhance cochlear mitochondrial function, alleviate oxidative stress, and regulate apoptosis. The association between SNHL and social isolation as well as cognitive decline underscores the necessity for innovative therapeutic modalities addressing yet undiscovered mechanisms. Translating findings from animal models to human studies will validate these findings, offering a synergistic approach to effectively manage DM-associated co-morbidities such as hearing impairment.

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Nanodelivery of antioxidant Agents: A promising strategy for preventing sensorineural hearing loss

Hajmohammadi,

Bagher,

Taghizadeh-Hesary

et al. 2024

European Journal of Pharmaceutics and Biopharmaceutics

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Upregulation of thioredoxin contributes to inhibiting diabetic hearing impairment

Cited by 8 publications

References 39 publications

Thioredoxin-1 decreases alpha-synuclein induced by MPTP through promoting autophagy-lysosome pathway

Thioredoxin-1 decreases alpha-synuclein induced by MPTP through promoting autophagy-lysosome pathway

Diabetes mellitus, hearing loss, and therapeutic interventions: A systematic review of insights from preclinical animal models

Nanodelivery of antioxidant Agents: A promising strategy for preventing sensorineural hearing loss

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