Heat shock response in noise-induced hearing loss: effects of alanyl-glutamine dipeptide supplementation on heat shock proteins status

Marcos Soares,Analu B Dos Santos,Tainara M Weich,Gabriela Gomes Mânica,Paulo Ivo Homem De Bittencourt,Mirna Stela Ludwig,Thiago Gomes Heck

doi:10.1016/j.bjorl.2019.04.012

Abstract

IntroductionThe 72kDa heat shock protein, HSP72, located intracellularly provides cochlear cytoprotective and anti-inflammatory roles in the inner ear during stressful noise challenges. The expression of intracellular HSP72 (iHSP72) can be potentiated by alanyl-glutamine dipeptide supplementation. Conversely, these proteins act as pro-inflammatory signals in the extracellular milieu (eHSP72). ObjectiveWe explore whether noise-induced hearing loss promotes both intracellular and extracellular HSP72 heat shock response alterations, and if alanyl-glutamine dipeptide supplementation could modify heat shock response and prevent hearing loss. MethodsFemale 90 day-old Wistar rats (n=32) were randomly divided into four groups: control, noise-induced hearing loss, treated with alanyl-glutamine dipeptide and noise-induced hearing loss plus alanyl-glutamine dipeptide. Auditory brainstem responses were evaluated before noise exposure (124dB SPL for 2h) and 14days after. Cochlea, nuclear cochlear complex and plasma samples were collected for the measurement of intracellular HSP72 and extracellular HSP72 by a high-sensitivity ELISA kit. ResultsWe found an increase in both iHSP72 and eHSP72 levels in the noise-induced hearing loss group, which was alleviated by alanyl-glutamine dipeptide treatment. Furthermore, H-index of HSP72 (plasma/cochlea eHSP72/iHSP72 ratio) was increased in the noise-induced hearing loss group, but prevented by alanyl-glutamine dipeptide treatment, although alanyl-glutamine dipeptide had no effect on auditory threshold. ConclusionsOur data indicates that cochlear damage induced by noise exposure is accompanied by local and systemic heat shock response markers. Also, alanyl-glutamine reduced stress markers even though it had no effect on noise-induced hearing loss. Finally, plasma levels of 72kDa heat shock proteins can be used as a biomarker of auditory stress after noise exposure.

Highlights

The 72 kDa heat shock protein, HSP72, located intracellularly provides cochlear cytoprotective and anti-inflammatory roles in the inner ear during stressful noise challenges
In the present study using rats, we investigated whether noise exposition could induce Heat Shock Response (HSR) locally in the cochlea and systemically
Increases were observed in both plasma/cochlear HSP70 ratio (Fig. 4A) and plasma/nuclear cochlear complex HSP70 ratio (Fig. 4B)

Summary

Introduction

The 72 kDa heat shock protein, HSP72, located intracellularly provides cochlear cytoprotective and anti-inflammatory roles in the inner ear during stressful noise challenges. The expression of intracellular HSP72 can be potentiated by alanyl-glutamine dipeptide supplementation. These proteins act as pro-inflammatory signals in the extracellular milieu. Objective: We explore whether noise-induced hearing loss promotes both intracellular and extracellular HSP72 heat shock response alterations, and if alanyl-glutamine dipeptide supplementation could modify heat shock response and prevent hearing loss. Noise is the main etiological risk factor for hearing damage, it is estimated that 10% of the human population is exposed to excessive sound pressure, at levels that may induce auditory injury. Noise-Induced Hearing Loss (NIHL) is the most prevalent occupational disease in the US, with 22 million workers exposed to high levels of noise, requiring close to 240 million dollars in hearing loss treatment.1---3.

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