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Bernd Fritzsch, Karen L Elliott
All craniate chordates have inner ears with hair cells that receive input from the brain by cholinergic centrifugal fibers, the so-called inner ear efferents (IEEs). Comparative data suggest that IEEs derive from facial branchial motor (FBM) neurons that project to the inner ear instead of facial muscles. Developmental data showed that IEEs develop adjacent to FBMs and segregation from IEEs might depend on few transcription factors uniquely associated with IEEs. Like other cholinergic terminals in the peripheral nervous system (PNS), efferent terminals signal on hair cells through nicotinic acetylcholine channels, likely composed out of alpha 9 and alpha 10 units (Chrna9, Chrna10)...
2017: Frontiers in Cellular Neuroscience
Jun-Ping Bai, Iman Moeini-Naghani, Sheng Zhong, Fang-Yong Li, Shumin Bian, Fred J Sigworth, Joseph Santos-Sacchi, Dhasakumar Navaratnam
Prestin in the lateral membrane of outer hair cells, is responsible for electromotility (EM) and a corresponding nonlinear capacitance (NLC). Prestin's voltage sensitivity is influenced by intracellular chloride. A regulator of intracellular chloride is a stretch-sensitive, non-selective conductance within the lateral membrane, GmetL. We determine that prestin itself possesses a stretch-sensitive, non-selective conductance that is largest in the presence of thiocyanate ions. This conductance is independent of the anion transporter mechanism...
April 19, 2017: Scientific Reports
Verónica Lamas, José M Juiz, Miguel A Merchán
The auditory cortex (AC) dynamically regulates responses of the Organ of Corti to sound through descending connections to both the medial (MOC) and lateral (LOC) olivocochlear efferent systems. We have recently provided evidence that AC has a reinforcement role in the responses to sound of the auditory brainstem nuclei. In a molecular level, we have shown that descending inputs from AC are needed to regulate the expression of molecules involved in outer hair cell (OHC) electromotility control, such as prestin and the α10 nicotinic acetylcholine receptor (nAchR)...
March 2017: Hearing Research
Patrick Vizeli, Yasmin Schmid, Katharina Prestin, Henriette E Meyer Zu Schwabedissen, Matthias E Liechti
In vitro studies showed that CYP2C19, CYP2B6, and CYP1A2 contribute to the metabolism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) to 3,4-methylenedioxyamphetamine (MDA). However, the role of genetic polymorphisms in CYP2C19, CYP2B6, and CYP1A2 in the metabolism of MDMA in humans is unknown. The effects of genetic variants in these CYP enzymes on the pharmacokinetics and pharmacodynamics of MDMA were characterized in 139 healthy subjects (69 male, 70 female) in a pooled analysis of eight double-blind, placebo-controlled studies...
January 20, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Yuan-Yuan Li, Zhen Liu, Fei-Yan Qi, Xin Zhou, Peng Shi
Molecular basis for mammalian echolocation has been receiving much concerns. Recent findings on the parallel evolution of prestin sequences among echolocating bats and toothed whales suggest that adaptations for high-frequency hearing have occurred during the evolution of echolocation. Here, we report that although the species tree for echolocating bats emitting echolocation calls with frequency modulated (FM) sweeps is paraphyletic, prestin exhibits similar functional changes between FM bats. Site-directed mutagenesis shows that the amino acid 308S in FM bats is responsible for the similar functional changes of prestin We strongly support that the occurrence of serine at position 308 is a case of hemiplasy, caused by incomplete lineage sorting of an ancestral polymorphism...
January 2017: Molecular Biology and Evolution
Gilda M Kalinec, Channy Park, Pru Thein, Federico Kalinec
HEI-OC1 is one of the few mouse auditory cell lines available for research purposes. Originally proposed as an in vitro system for screening of ototoxic drugs, these cells have been used to investigate drug-activated apoptotic pathways, autophagy, senescence, mechanism of cell protection, inflammatory responses, cell differentiation, genetic and epigenetic effects of pharmacological drugs, effects of hypoxia, oxidative and endoplasmic reticulum stress, and expression of molecular channels and receptors. Among other several important markers of cochlear hair cells, HEI-OC1 cells endogenously express prestin, the paradigmatic motor protein of outer hair cells...
2016: Journal of Visualized Experiments: JoVE
Kourosh Parham, Jonas Dyhrfjeld-Johnsen
HYPOTHESIS: At present there are no serum biomarkers available to monitor cochlear health in those at risk of hearing loss. Outer hair cells (OHCs) play an important role in cochlear function and are one of the cellular elements most vulnerable to damage, such as acoustic trauma. We hypothesized that an OHC-specific protein can serve as a biomarker for OHC damage in circulation. METHODS: After assessing auditory function, rats were exposed to intense octave band noise for 2 to 3 hours...
October 2016: Otology & Neurotology
Katharina Prestin, Maria Olbert, Janine Hussner, Tamara L Isenegger, Daniel G Gliesche, Kerstin Böttcher, Uwe Zimmermann, Henriette E Meyer Zu Schwabedissen
Mammalian nuclear receptors (NRs) are transcription factors regulating the expression of target genes that play an important role in drug metabolism, transport, and cellular signaling pathways. The orphan and structurally unique receptor small heterodimer partner 1 (syn NR0B2) is not only known for its modulation of drug response, but has also been reported to be involved in hepatocellular carcinogenesis. Indeed, previous studies show that NR0B2 is downregulated in human hepatocellular carcinoma, suggesting that NR0B2 acts as a tumor suppressor via inhibition of cellular growth and activation of apoptosis in this tumor entity...
2016: OncoTargets and Therapy
Fei Yu, Shuai Hao, Bo Yang, Yue Zhao, Jun Yang
We evaluated the role of iron deficiency (ID) without anemia on hearing function and cochlear pathophysiology of young rats before and after noise exposure. We used rats at developmental stages as an animal model to induce ID without anemia by dietary iron restriction. We have established this dietary restriction model in the rat that should enable us to study the effects of iron deficiency in the absence of severe anemia on hearing and ribbon synapses. Hearing function was measured on Postnatal Day (PND) 21 after induction of ID using auditory brainstem response (ABR)...
July 28, 2016: Nutrients
Anna Sofia Birke, Arnaud Javelle
In a recent paper published in the Biochemical Journal, Lolli et al. presented evidence that the C-terminal STAS (sulfate transporter and anti-sigma factor antagonist) domain of the motor protein prestin possesses an anion-binding site. This discovery might shed light on an aspect of the function of this mysterious and fascinating protein that is crucial for the human hearing system.
August 1, 2016: Biochemical Journal
David Thorn, Christoph Mamot, Fatime Krasniqi, Frank Metternich, Sven Prestin
The Ewing sarcoma family of tumors (ESFT) encompasses a group of highly aggressive, morphologically similar, malignant neoplasms sharing a common spontaneous genetic translocation that affect mostly children and young adults. These predominantly characteristic, small round-cell tumors include Ewing's sarcoma of the bone and soft tissue, as well as primitive neuroectodermal tumors (PNETs) involving the bone, soft tissue, and thoracopulmonary region (Askin's tumor). Extraosseous ESFTs are extremely rare, especially in the head and neck region, where literature to date consists of sporadic case reports and very small series...
2016: Sarcoma
Gunnar Alvan, Erik Berninger, Lars L Gustafsson, Kjell K Karlsson, Gilles Paintaud, Monique Wakelkamp
This review has the purpose to summarize concentration-effect studies made with quinine and to compare the effects on hearing between quinine and salicylate. Quinine and salicylate have roles in experimental hearing research and may induce pronounced and reversible hearing impairment when administered in sizeable doses. The quinine-induced increase in hearing threshold and its recovery can be analysed according to 'the psychophysical power function'. The power function is a special case of the Hill equation when the stimulus (e...
January 2017: Basic & Clinical Pharmacology & Toxicology
Robert Farkaš, Ludmila Pečeňová, Lucia Mentelová, Milan Beňo, Denisa Beňová-Liszeková, Silvia Mahmoodová, Václav Tejnecký, Otakar Raška, Pavel Juda, Silvie Svidenská, Matúš Hornáček, Bruce A Chase, Ivan Raška
The Drosophila salivary glands (SGs) were well known for the puffing patterns of their polytene chromosomes and so became a tissue of choice to study sequential gene activation by the steroid hormone ecdysone. One well-documented function of these glands is to produce a secretory glue, which is released during pupariation to fix the freshly formed puparia to the substrate. Over the past two decades SGs have been used to address specific aspects of developmentally-regulated programmed cell death (PCD) as it was thought that they are doomed for histolysis and after pupariation are just awaiting their fate...
August 2016: Development, Growth & Differentiation
Joseph Santos-Sacchi, Lei Song
In general, SLC26 solute carriers serve to transport a variety of anions across biological membranes. However, prestin (SLC26a5) has evolved, now serving as a motor protein in outer hair cells (OHCs) of the mammalian inner ear and is required for cochlear amplification, a mechanical feedback mechanism to boost auditory performance. The mechanical activity of the OHC imparted by prestin is driven by voltage and controlled by anions, chiefly intracellular chloride. Current opinion is that chloride anions control the Boltzmann characteristics of the voltage sensor responsible for prestin activity, including Qmax, the total sensor charge moved within the membrane, and Vh, a measure of prestin's operating voltage range...
June 7, 2016: Biophysical Journal
Michelle L Seymour, Lavanya Rajagopalan, Guillaume Duret, Matthew J Volk, Haiying Liu, William E Brownell, Fred A Pereira
Full expression of electromotility, generation of non-linear capacitance (NLC), and high-acuity mammalian hearing require prestin function in the lateral wall of cochlear outer hair cells (OHCs). Estimates of the number of prestin molecules in the OHC membrane vary, and a consensus has not emerged about the correlation between prestin expression and prestin-associated charge movement in the OHC. Using an inducible prestin-expressing cell line, we demonstrate that the charge density, but not the voltage at peak capacitance, directly correlates with the amount of prestin in the plasma membrane...
September 2016: Hearing Research
Mussie Araya, William E Brownell
The soft, thin membranes that envelop all living cells are 2D, nanoscale, fluid assemblies of phospholipids, sterols, proteins, and other molecules. Mechanical interactions between these components facilitate membrane function, a key example of which is ion flow mediated by the mechanical opening and closing of channels. Hearing and balance are initiated by the modulation of ion flow through mechanoreceptor channels in stereocilia membranes. Cochlear amplification by the outer hair cell involves modulation of ion movement by the membrane protein prestin...
2016: Methods in Molecular Biology
Michael G Nichols, Richard Hallworth
The advent of techniques for imaging solitary fluorescent molecules has made possible many new kinds of biological experiments. Here, we describe the application of single-molecule imaging to the problem of subunit stoichiometry in membrane proteins. A membrane protein of unknown stoichiometry, prestin, is coupled to the fluorescent enhanced green fluorescent protein (eGFP) and synthesized in the human embryonic kidney (HEK) cell line. We prepare adherent membrane fragments containing prestin-eGFP by osmotic lysis...
2016: Methods in Molecular Biology
Yasmin Schmid, Patrick Vizeli, Cédric M Hysek, Katharina Prestin, Henriette E Meyer Zu Schwabedissen, Matthias E Liechti
The role of genetic polymorphisms in cytochrome (CYP) 2D6 involved in the metabolism of 3,4-methylene-dioxymethamphetamine (MDMA, ecstasy) is unclear. Effects of genetic variants in CYP2D6 on the pharmacokinetics and pharmacodynamic effects of MDMA were characterized in 139 healthy individuals (70 men, 69 women) in a pooled analysis of eight double-blind, placebo-controlled crossover studies. In CYP2D6 poor metabolizers, the maximum concentrations (Cmax) of MDMA and its active metabolite 3,4-methylene-dioxyamphetamine were +15 and +50% higher, respectively, compared with extensive metabolizers and the Cmax of the inactive metabolite 4-hydroxy-3-methoxymethamphetamine was 50-70% lower...
August 2016: Pharmacogenetics and Genomics
Jian Zhang, Ziyi Liu, Aoshuang Chang, Jie Fang, Yuqin Men, Yong Tian, Xiaomei Ouyang, Denise Yan, Aizhen Zhang, Xiaoyang Sun, Jie Tang, Xuezhong Liu, Jian Zuo, Jiangang Gao
Prestin is critical to OHC somatic motility and hearing sensitivity in mammals. Several mutations of the human SLC26A5 gene have been associated with deafness. However, whether the IVS2-2A>G mutation in the human SLC26A5 gene causes deafness remains controversial. In this study, we created a mouse model in which the IVS2-2A>G mutation was introduced into the mouse Slc26a5 gene by gene targeting. The homozygous Slc26a5 mutant mice were viable and fertile and displayed normal hearing sensitivity by ABR threshold analysis...
August 2016: Mutation Research
Meng Wu, John F Heneghan, David H Vandorpe, Laura I Escobar, Bai-Lin Wu, Seth L Alper
Genetic deficiency of the SLC26A1 anion exchanger in mice is known to be associated with hyposulfatemia and hyperoxaluria with nephrolithiasis, but many aspects of human SLC26A1 function remain to be explored. We report here the functional characterization of human SLC26A1, a 4,4'-diisothiocyanato-2,2'-stilbenedisulfonic acid (DIDS)-sensitive, electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, bicarbonate, thiosulfate, and (with divergent properties) chloride. Human SLC26A1-mediated anion exchange differs from that of its rodent orthologs in its stimulation by alkaline pHo and inhibition by acidic pHo but not pHi and in its failure to transport glyoxylate...
August 2016: Pflügers Archiv: European Journal of Physiology
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