scholarly journals G6PD overexpression protects from oxidative stress and age‐related hearing loss

Aging Cell ◽  
2020 ◽  
Vol 19 (12) ◽  
Author(s):  
Jose M. Bermúdez‐Muñoz ◽  
Adelaida M. Celaya ◽  
Sara Hijazo‐Pechero ◽  
Jing Wang ◽  
Manuel Serrano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Mitochondria-Targeted Antioxidants for Treatment of Hearing Loss: A Systematic Review

Antioxidants ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 109 ◽  
Author(s):  
Chisato Fujimoto ◽  
Tatsuya Yamasoba
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Mitochondrial Dysfunction ◽  
Cell Lines ◽  
Mitochondrial Gene ◽  
Protective Effects ◽  
Drug Induced ◽  
Age Related ◽  
Cochlear Damage ◽  
Age Related Hearing Loss

Mitochondrial dysfunction is associated with the etiologies of sensorineural hearing loss, such as age-related hearing loss, noise- and ototoxic drug-induced hearing loss, as well as hearing loss due to mitochondrial gene mutation. Mitochondria are the main sources of reactive oxygen species (ROS) and ROS-induced oxidative stress is involved in cochlear damage. Moreover, the release of ROS causes further damage to mitochondrial components. Antioxidants are thought to counteract the deleterious effects of ROS and thus, may be effective for the treatment of oxidative stress-related diseases. The administration of mitochondria-targeted antioxidants is one of the drug delivery systems targeted to mitochondria. Mitochondria-targeted antioxidants are expected to help in the prevention and/or treatment of diseases associated with mitochondrial dysfunction. Of the various mitochondria-targeted antioxidants, the protective effects of MitoQ and SkQR1 against ototoxicity have been previously evaluated in animal models and/or mouse auditory cell lines. MitoQ protects against both gentamicin- and cisplatin-induced ototoxicity. SkQR1 also provides auditory protective effects against gentamicin-induced ototoxicity. On the other hand, decreasing effect of MitoQ on gentamicin-induced cell apoptosis in auditory cell lines has been controversial. No clinical studies have been reported for otoprotection using mitochondrial-targeted antioxidants. High-quality clinical trials are required to reveal the therapeutic effect of mitochondria-targeted antioxidants in terms of otoprotection in patients.

scholarly journals Role of Oxidative Stress in the Senescence Pattern of Auditory Cells in Age-Related Hearing Loss

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1497
Author(s):  
Luz del Mar Rivas-Chacón ◽  
Sofía Martínez-Rodríguez ◽  
Raquel Madrid-García ◽  
Joaquín Yanes-Díaz ◽  
Juan Ignacio Riestra-Ayora ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Cell Damage ◽  
Stria Vascularis ◽  
Organ Of Corti ◽  
Age Related ◽  
Age Related Hearing Loss

Age-related hearing loss (ARHL) is an increasing and gradual sensorineural hearing dysfunction. Oxidative stress is an essential factor in developing ARHL; additionally, premature senescence of auditory cells induced by oxidative stress can produce hearing loss. Hydrogen peroxide (H2O2) represents a method commonly used to generate cellular senescence in vitro. The objective of the present paper is to study H2O2-induced senescence patterns in three auditory cell lines (House Ear Institute-Organ of Corti 1, HEI-OC1; organ of Corti, OC-k3, and stria vascularis, SV-k1 cells) to elucidate the intrinsic mechanisms responsible for ARHL. The auditory cells were exposed to H2O2 at different concentrations and times. The results obtained show different responses of the hearing cells concerning cell growth, β-galactosidase activity, morphological changes, mitochondrial activation, levels of oxidative stress, and other markers of cell damage (Forkhead box O3a, FoxO3a, and 8-oxoguanine, 8-oxoG). Comparison between the responses of these auditory cells to H2O2 is a helpful method to evaluate the molecular mechanisms responsible for these auditory cells’ senescence. Furthermore, this in vitro model could help develop anti-senescent therapeutic strategies for the treatment of AHRL.

scholarly journals Activation of the NRF2 pathway in Keap1-knockdown mice attenuates progression of age-related hearing loss

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Tetsuya Oishi ◽  
Daisuke Matsumaru ◽  
Nao Ota ◽  
Hiroshi Kitamura ◽  
Tianxiang Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Target Genes ◽  
Negative Regulator ◽  
Nrf2 Pathway ◽  
Expression Levels ◽  
Age Related ◽  
Pathway Activation ◽  
Brainstem Response ◽  
Age Related Hearing Loss

AbstractAge-related hearing loss (AHL) is a progressive sensorineural hearing loss in elderly people. Although no prevention or treatments have been established for AHL, recent studies have demonstrated that oxidative stress is closely related to pathogenesis of AHL, suggesting that suppression of oxidative stress leads to inhibition of AHL progression. NRF2 is a master transcription factor that regulates various antioxidant proteins and cytoprotection factors. To examine whether NRF2 pathway activation prevents AHL, we used Keap1-knockdown (Keap1FA/FA) mice, in which KEAP1, a negative regulator of NRF2, is decreased, resulting in the elevation of NRF2 activity. We compared 12-month-old Keap1FA/FA mice with age-matched wild-type (WT) mice in the same breeding colony. In the Keap1FA/FA mice, the expression levels of multiple NRF2 target genes were verified to be significantly higher than the expression levels of these genes in the WT mice. Histological analysis showed that cochlear degeneration at the apical and middle turns was ameliorated in the Keap1FA/FA mice. Auditory brainstem response (ABR) thresholds in the Keap1FA/FA mice were significantly lower than those in the WT mice, in particular at low–mid frequencies. Immunohistochemical detection of oxidative stress markers suggested that oxidative stress accumulation was attenuated in the Keap1FA/FA cochlea. Thus, we concluded that NRF2 pathway activation protects the cochlea from oxidative damage during aging, in particular at the apical and middle turns. KEAP1-inhibiting drugs and phytochemicals are expected to be effective in the prevention of AHL.

Oxidative Stress, Inflammation, and Autophagic Stress as the Key Mechanisms of Premature Age-Related Hearing Loss in SAMP8 Mouse Cochlea

2012 ◽  
Vol 16 (3) ◽  
pp. 263-274 ◽  
Author(s):  
Julien Menardo ◽  
Yong Tang ◽  
Sabine Ladrech ◽  
Marc Lenoir ◽  
François Casas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Samp8 Mouse ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Effect of SOD2 methylation on mitochondrial DNA4834-bp deletion mutation in marginal cells under oxidative stress

2019 ◽  
Author(s):  
Jun Li ◽  
Xiang Dai ◽  
Xuelian He ◽  
Rong Yang ◽  
Zhongfang Xia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Methylation Level ◽  
Copy Number ◽  
Deletion Mutation ◽  
Physical And Mental Health ◽  
Mt Dna ◽  
Age Related ◽  
Marginal Cells ◽  
Age Related Hearing Loss

Presbycusis, or age-related hearing loss, is a prevalent disease that severely affects the physical and mental health of the elderly. Oxidative stress and mitochondrial (mt)DNA deletion mutation are considered as major factors in the pathophysiology of age-related hearing loss. The 4977-bp deletion in human mtDNA (common deletion, corresponding to the 4834-bp mtDNA deletion in rats) is suggested to be closely associated with the pathogenesis of age-related hearing loss. Superoxide dismutase 2 (SOD2), an isoform of SOD that is exclusively expressed in the intracellular mitochondrial matrix, plays a crucial role in oxidative resistance against mitochondrial superoxide. Previous research has shown that methylation of the promoter region of the SOD2 gene decreased the expression of SOD2 in marginal cells (MCs) extracted from the inner ear of rats subjected to D-galactose-induced mtDNA4834 deletion. However, the relationship between SOD2 methylation and mtDNA4834 deletion under oxidative stress remains to be elucidated. Herein, an oxidative damage model was established in the extracted MCs using hydrogen peroxide (H2O2), which increased the methylation level of SOD2 and the copy number of mtDNA4834 mutation in MCs. Decreasing the methylation level of SOD2 using 5-azacytidine, a DNA methylation inhibitor, reduced oxidative stress and the copy number of mtDNA4834 mutation and inhibited H2O2-induced apoptosis. The present work demonstrates that decreasing the methylation of SOD2 suppresses the mtDNA4834 deletion in MCs under oxidative stress and provides potential insights to the intervention therapy of aging-related hearing loss.

scholarly journals Long noncoding RNA Gm44593 attenuates oxidative stress from age-related hearing loss by regulating miR-29b/WNK1

Bioengineered ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 573-582
Author(s):  
Qian Li ◽  
Yanzi Zang ◽  
Zhanwei Sun ◽  
Wenqi Zhang ◽  
Hongjian Liu
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Down-regulation of Cav1.3 in auditory pathway promotes age-related hearing loss by enhancing calcium-mediated oxidative stress in male mice

Aging ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 6490-6502 ◽  
Author(s):  
Fan Qi ◽  
Rongsheng Zhang ◽  
Jin Chen ◽  
Fei Zhao ◽  
Yanbo Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Auditory Pathway ◽  
Male Mice ◽  
Down Regulation ◽  
Age Related ◽  
Age Related Hearing Loss
Sign in / Sign up

Export Citation Format

Share Document