Prestin

INTRODUCTION: Occupational noise exposure is a major public health concern, impacting a large workforce worldwide. In this study, we sought to evaluate the serum concentrations of prestin, a cochlear protein that diminishes following noise exposure, and otolin-1, a protein secreted into the bloodstream subsequent to inner ear damage, among three diverse professional categories, each exposed to varying degrees of noise. Helicopter emergency medical service (HEMS) pilots and construction workers were considered high-risk groups due to their elevated exposure to occupational noise, whereas office workers were regarded as a low-risk group, reflecting their comparatively minimal noise exposure...

Mammalian SLC26 proteins are membrane-based anion transporters that belong to the large SLC26/SulP family, and many of their variants are associated with hereditary diseases. Recent structural studies revealed a strikingly similar homodimeric molecular architecture for several SLC26 members, implying a shared molecular principle. Now a new question emerges as to how these structurally similar proteins execute diverse physiological functions. In this study we sought to identify the common vs. distinct molecular mechanism among the SLC26 proteins using both naturally occurring and artificial missense changes introduced to SLC26A4, SLC26A5, and SLC26A9...

HYPOTHESIS: Cyclodextrin (CDX)-induced serum prestin burst is not dependent on outer hair cell (OHC) loss. BACKGROUND: Serum prestin has been proposed as a biomarker for ototoxicity. We recently used an automated Western approach to quantify serum prestin changes in a newly introduced model of CDX ototoxicity. To gain insights into prestin as a biomarker, here we further characterize serum prestin in the CDX model. METHODS: Guinea pigs were treated with 750, 3,000, or 4,000 mg/kg CDX, and serum samples were obtained through up to 15 weeks after exposure...

OBJECTIVES: To determine if blood prestin level changes after exposure to music at high sound pressure levels, and if this change is associated with temporary threshold shift (TTS) and/or changes in distortion product (DP) amplitude. DESIGN: Participants were exposed to pop-rock music at 100 dBA for 15 min monaurally through headphones. Pure-tone audiometry, DP amplitude, and blood prestin level were measured before and after exposure. RESULTS: Fourteen adults (9 women; age range: 20 to 54 years, median age = 31 [Interquartile ratio = 6...

Pendrin and prestin are evolutionary-conserved membrane proteins that are essential for normal hearing. Dysfunction of these proteins results in hearing loss in humans, and numerous deafness-associated pendrin and prestin variants have been identified in patients. However, the pathogenic impacts of many of these variants are ambiguous. Here, we report results from our ongoing efforts to experimentally characterize pendrin and prestin variants using in vitro functional assays. With previously established fluorometric anion transport assays, we determined that many of the pendrin variants identified on transmembrane (TM) 10, which contains the essential anion binding site, and on the neighboring TM9 within the core domain resulted in impaired anion transport activity...

OBJECTIVE: Prestin is an outer hair cell (OHC) protein responsible for increasing cochlear sensitivity and has been proposed as a biomarker. We aimed to evaluate whether the serum prestin level is related to the severity of chronic sensorineural hearing loss (SNHL). METHODS: Ninety subjects were recruited from the patient base at Samarra public hospitals and clinics in Iraq from January to October of 2022. They were divided into three groups equally: a group of healthy people without hearing loss (G0), a group with moderate SNHL (G1), and a group with severe SNHL (G2)...

DFNB61 is a recessively inherited nonsyndromic hearing loss caused by mutations in SLC26A5, the gene that encodes the voltage-driven motor protein, prestin. Prestin is abundantly expressed in the auditory outer hair cells that mediate cochlear amplification. Two DFNB61-associated SLC26A5 variants, p.W70X and p.R130S, were identified in patients who are compound heterozygous for these nonsense and missense changes (SLC26A5W70X/R130S ). Our recent study showed that mice homozygous for p.R130S (Slc26a5R130S/R130S ) suffer from hearing loss that is ascribed to significantly reduced motor kinetics of prestin...

UNLABELLED: The function of prestin (SLC26a5), an anion transport family member, has evolved to enhance auditory sensitivity and frequency selectivity by providing mechanical feedback via outer hair cells (OHC) into the organ of Corti. The frequency extent of this boost is governed by the voltage-dependent kinetics of the protein's charge movements, otherwise known as nonlinear capacitance (NLC) that we measure in membrane patches under voltage clamp. Here we extend our previous studies on guinea pig OHCs by studying the frequency response of NLC in the mouse OHC, a species with higher frequency auditory needs...

Pendrin and prestin are evolutionary conserved membrane proteins that are essential for normal hearing. Pendrin is an anion transporter required for normal development and maintenance of ion homeostasis in the inner ear, while prestin is a voltage-dependent motor responsible for cochlear amplification essential for high sensitivity and frequency selectivity of mammalian hearing. Dysfunction of these proteins result in hearing loss in humans, and numerous deafness-associated pendrin and prestin variants have been identified in patients...

OBJECTIVE: The objective of this study is to demonstrate any inner ear injury caused by drilling in mastoid surgery with prestin, outer hair cell motor protein specific to the cochlea. METHODS: The patients with chronic otitis media requiring mastoidectomy (n = 21) and myringoplasty (n = 21) were included. Serum prestin level obtained from blood samples was measured before surgery and on postoperative days 0, 3, and 7 using Human Prestin (SLC26A5) ELISA Kit...

The outer hair cells (OHCs) of the mammalian cochlea are the mediators of an active, nonlinear electromechanical process necessary for sensitive, frequency specific hearing. The membrane protein prestin conveys to the OHC a piezoelectric-like behavior hypothesized to actuate a high frequency, cycle-by-cycle conversion of electrical to mechanical energy to boost cochlear responses to low-level sound. This hypothesis has been debated for decades, and we address two key remaining issues: the influence of the rate dependence of conformal changes in prestin and the OHC transmembrane impedance...

Otoacoustic emissions (OAEs) are a non-invasive metric of cochlear function. Studies of OAEs in musicians have yielded mixed results, ranging from evidence of diminished OAEs in musicians-suggesting noise-induced hearing loss-to no difference when compared to non-musicians, or even a trend for stronger OAEs in musicians. The goal of this study was to use a large sample of college students with normal hearing (n = 160) to compare OAE SNRs in musicians and non-musicians and to explore potential effects of training recency and noise exposure on OAEs in these cohorts...

Prestin responds to transmembrane voltage fluctuations by changing its cross-sectional area, a process underlying the electromotility of outer hair cells and cochlear amplification. Prestin belongs to the SLC26 family of anion transporters yet is the only member capable of displaying electromotility. Prestin's voltage-dependent conformational changes are driven by the putative displacement of residue R399 and a set of sparse charged residues within the transmembrane domain, following the binding of a Cl- anion at a conserved binding site formed by the amino termini of the TM3 and TM10 helices...

The outstanding acuity of the mammalian ear relies on cochlear amplification, an active mechanism based on the electromotility (eM) of outer hair cells. eM is a piezoelectric mechanism generated by little-understood, voltage-induced conformational changes of the anion transporter homolog prestin (SLC26A5). We used a combination of molecular dynamics (MD) simulations and biophysical approaches to identify the structural dynamics of prestin that mediate eM. MD simulations showed that prestin samples a vast conformational landscape with expanded (ES) and compact (CS) states beyond previously reported prestin structures...

Echolocation, the detection of objects by means of sound waves, has evolved independently in diverse animals. Echolocators include not only mammals such as toothed whales and yangochiropteran and rhinolophoid bats but also Rousettus fruit bats, as well as two bird lineages, oilbirds and swiftlets. In whales and yangochiropteran and rhinolophoid bats, positive selection and molecular convergence has been documented in key hearing-related genes, such as prestin ( SLC26A5 ), but few studies have examined these loci in other echolocators...

DFNB61 is a recessively inherited nonsyndromic hearing loss caused by mutations in SLC26A5 , the gene that encodes the voltage-driven motor protein, prestin. Prestin is abundantly expressed in the auditory outer hair cells that mediate cochlear amplification. Two DFNB61-associated SLC26A5 variants, p.W70X and p.R130S, were identified in patients who are compound heterozygous for these nonsense and missense changes ( SLC26A5 W70X/R130S ). Our recent study showed that mice homozygous for p.R130S ( Slc26a5 R130S/R130S ) suffer from hearing loss that is ascribed to significantly reduced motor kinetics of prestin...

Auditory frequency coding is place-specific, which depends on the mechanical coupling of the basilar membrane-outer hair cell (OHC)-tectorial membrane network. Prestin-based OHC electromotility improves cochlear frequency selectivity and sensitivity. Cochlear amplification determines the frequency coding wherein discrete sound frequencies find a 'best' place along the cochlear length. Loss of OHC is the leading cause of age-related hearing loss (ARHL) and is the most common cause of sensorineural hearing loss and compromised speech perception...

Cholesterol contributes to neuronal membrane integrity, supports membrane protein clustering and function, and facilitates proper signal transduction. Extensive evidence has shown that cholesterol imbalances in the central nervous system occur in aging and in the development of neurodegenerative diseases. In this work, we characterize cholesterol homeostasis in the inner ear of young and aged mice as a new unexplored possibility for the prevention and treatment of hearing loss. Our results show that cholesterol levels in the inner ear are reduced during aging, an effect that is associated with an increased expression of the cholesterol 24-hydroxylase (CYP46A1), the main enzyme responsible for cholesterol turnover in the brain...

HYPOTHESIS: Ototoxin cyclodextrin (CDX) will induce a burst in serum prestin when quantified with automated Western blot analysis. BACKGROUND: In the clinical realm, we primarily rely on audiological measures for diagnosis and surveillance of sensorineural hearing loss (SNHL) and have limited therapeutic options. We have proposed a blood-based biomarker approach to overcome this challenge by measuring the outer hair cell's (OHC) electromotile protein, prestin, in the blood...

Normal hearing is associated with cochlear nonlinearity. When two tones (f1 and f2) are presented, the intracochlear response contains additional components that can be recorded from the ear canal as distortion product otoacoustic emissions (DPOAEs). Although the most prominent intermodulation distortion component is at 2f1-f2, other cubic distortion products are also generated. Because these measurements are noninvasive, they are used in humans and in animal models to detect hearing loss. This study evaluated how loss of sensitivity affects DPOAEs with frequencies above and below the stimulating primaries, i...