Increased Sensitivity to Noise-Induced Hearing Loss by Blockade of Endogenous PI3K/Akt Signaling

Chen, Jun; Hu, Yuan; Talaska, Andra E.; Hill, Kayla; Sha, Su-Hua

doi:10.1007/s10162-015-0508-x

Cited by 41 publications

(37 citation statements)

References 30 publications

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“…Endogenous PI3K/Akt signaling is an intrinsic inner ear protective mechanism that plays an active role in maintaining hair cell (HC) viability throughout life. A decrease in PI3K signaling correlated with a reduction in HC survival capacity with age .…”

Section: Discussionmentioning

confidence: 99%

microRNAs in sudden hearing loss

et al. 2019

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Objectives: To compare the circulating microRNA (miRNA) expression profiles between sudden sensory neural hearing loss (SSNHL) patients and age-matched normal hearing controls.Study Design: Prospective cohort multi-center study. Methods: Patients presenting within 28 days of onset of SSNHL were prospectively recruited along with contemporaneous age-matched controls. Pooled sera of four patient (n = 09, mean age = 53.0 years; 07, 55.0; 10, 52.9; 10, 51.6) and two control (09, 51.2 and 03, 50.0) groups were assessed using a TaqMan Low Density Array. The patients' sera were also divided into two pools, untreated (04, 57.7) and treated (32, 52.6) for additional analysis. miRNA expression level was derived from cycle threshold (Ct) values normalized to a global mean. Inter-group mean Ct differences with fold changes ≥2.0 and ≤0.5 at P < .05 were considered significant. Bioinformatic databases were used to identify putative target mRNAs or validated genes and their functional annotations.Results: Thirty-six SSNHL patients (mean age 53.0 AE standard deviation (SD) 15.2 years) and 12 controls (50.9 AE 11.9) were studied. Eight miRNAs hsa-miR-590-5p/ -186-5p/ -195-5p/ -140-3p/ -128-3p/ -132-3p/ -375-3p, and -30a-3p were identified as significantly differentially expressed in SSNHL patients. Most of these miRNAs were abundantly identified in the nervous system and the putative target messenger RNAs (mRNAs) were enriched in signaling pathways such as phosphatidyl inositol 3 kinase/protein Kinase B (PI3K/Akt), Ras and mitogen-activated protein kinase (MAPK).Conclusion: These findings suggest the possible cellular signaling pathways that underlie the disruption of auditory signal transmission in SSNHL.

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Section: Discussionmentioning

confidence: 99%

microRNAs in sudden hearing loss

et al. 2019

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“…Another well-recognized survival signaling pathway is mediated by phosphatidylinositol 3 kinase (PI3K), protein kinase c (PKC) and protein kinase B (also known as AKT), which can also be activated by growth factors. Chen et al (2015) found that blocking PI3K/AKT signaling increased sensitivity to NIHL in animals.…”

Section: Survival Signaling and The Negative Regulation Of Hc Damagementioning

confidence: 99%

Cellular mechanisms of noise-induced hearing loss

Kurabi¹,

Keithley²,

Housley³

et al. 2017

Hearing Research

253

200

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Exposure to intense sound or noise can result in purely temporary threshold shift (TTS), or leave a residual permanent threshold shift (PTS) along with alterations in growth functions of auditory nerve output. Recent research has revealed a number of mechanisms that contribute to noise-induced hearing loss (NIHL). The principle cause of NIHL is damage to cochlear hair cells and associated synaptopathy. Contributions to TTS include reversible damage to hair cell (HC) stereocilia or synapses, while moderate TTS reflects protective purinergic hearing adaptation. PTS represents permanent damage to or loss of HCs and synapses. While the substrates of HC damage are complex, they include the accumulation of reactive oxygen species and the active stimulation of intracellular stress pathways, leading to programmed and/or necrotic cell death. Permanent damage to cochlear neurons can also contribute to the effects of NIHL, in addition to HC damage. These mechanisms have translational potential for pharmacological intervention and provide multiple opportunities to prevent HC damage or to rescue HCs and spiral ganglion neurons that have suffered injury. This paper reviews advances in our understanding of cellular mechanisms that contribute to NIHL and their potential for therapeutic manipulation.

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“…In relation to the effect of the use of siRNA in the cochlear hair cells gene expression, Mukherjea et al [22][23][24] observed a silencing rate of 70% for the NADPH oxidase 3 (NOX3) gene after siRNA trans-tympanic injection. In addition, Chen et al [25] observed a decrease of 30% in the p85α gene expression in hair cells of animals previously submitted to siRNA intra-tympanic injection and after noise exposure. These data corroborated our results, since that the trans-tympanic injection performed in this study was able to reduce the Tnfα gene expression to 26.31%, with a silencing rate of 74.1% observed after noise exposure comparing the control.…”

Section: Discussionmentioning

confidence: 98%

New Insights on the Effect of TNF Alpha Blockade by Gene Silencing in Noise-Induced Hearing Loss

Rodrigues

Bachi

Silva

et al. 2020

IJMS

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Noise exposure represents the second most common cause of acquired sensorineural hearing loss and we observed that tumor necrosis factor α (TNFα) was involved in this context. The effect of Tnfα gene silencing on the expression profile related to the TNFα metabolic pathway in an experimental model of noise-induced hearing loss had not previously been studied. Methods: Single ears of Wistar rats were pretreated with Tnfα small interfering RNA (siRNA) by trans-tympanic administration 24 h before they were exposed to white noise (120 dBSPL for three hours). After 24 h of noise exposure, we analyzed the electrophysiological threshold and the amplitude of waves I, II, III, and IV in the auditory brain response click. In addition, qRT-PCR was performed to evaluate the TNFα metabolic pathway in the ears submitted or not to gene silencing. Results: Preservation of the electrophysiological threshold and the amplitude of waves was observed in the ears submitted to gene silencing compared to the ears not treated. Increased anti-apoptotic gene expression and decreased pro-apoptotic gene expression were found in the treated ears. Conclusion: Our results allow us to suggest that the blockade of TNFα by gene silencing was useful to prevent noise-induced hearing loss.

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Increased Sensitivity to Noise-Induced Hearing Loss by Blockade of Endogenous PI3K/Akt Signaling

Cited by 41 publications

References 30 publications

microRNAs in sudden hearing loss

microRNAs in sudden hearing loss

Cellular mechanisms of noise-induced hearing loss

New Insights on the Effect of TNF Alpha Blockade by Gene Silencing in Noise-Induced Hearing Loss

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