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Molecular Mechanisms in Noise-Induced Hearing Loss

噪声性听力损失的分子机制

基本信息

批准号：
8035320
负责人：
Su-Hua Sha
金额：
$ 35.59万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8035320
关键词：
5&apos -AMP-activated protein kinase Actins Address Affect Apoptosis Apoptotic Attenuated Biochemical Calcium Calmodulin Cell Culture Techniques Cell Death Cell Line Cells Clostridium difficile Cochlea Complex Creatine Cytoskeleton Developed Countries F-Actin Goals Growth Factor Guanosine Triphosphate Phosphohydrolases Hair Cells Health Care Costs Hearing Individual Investigation Labyrinth Lead Link Measures Mediating Mitochondria Modeling Molecular Monomeric GTP-Binding Proteins NADPH Oxidase Noise Noise-Induced Hearing Loss Outer Hair Cells Pathway interactions Phosphorylation Pilot Projects Preventive Intervention Protein Kinase Proteins Quality of life RNA Interference Regulation Reporting Research Role Serine Signal Transduction Staining method Stains Stress Testing Time Toxin Translations Trauma Work base design disability hearing impairment human FRAP1 protein in vitro Model in vivo inhibitor/antagonist innovation insight mTOR Signaling Pathway novel polymerization research study response

项目摘要

Noise-induced hearing loss is a major cause of acquired hearing deficits and one of the most frequent work-related disabilities in industrialized countries. The long term goal of this research is to understand the molecular mechanisms leading to noise-induced hearing loss. Based on exciting preliminary results on a signaling cascade initiated by energy depletion after noise exposure, the hypothesis is presented that transient energy depletion is an initial key factor in noise trauma. Transient energy depletion activates small GTPase pathways, which, in turn, lead to the destruction of F-actin in outer hair cells. Transient energy depletion also initiates mitochondria-mediated cell death, and blocks mTOR signaling pathways which normally serve as survival functions. In addition to the in-vivo studies, we are introducing a novel in-vitro model of energy depletion in an inner ear cell line to study specific aspects of the molecular pathways suspected in noise-induced hearing loss. The results of this project will lead to new insight into mechanisms of noise trauma. In addition, the results of this project may direct the design of novel interventions for the prevention of noise-induced hearing loss benefiting the quality of life of individuals and reducing health care costs.

噪声引起的听力损失是后天性听力缺陷的主要原因，也是工业化国家最常见的与工作有关的残疾之一。这项研究的长期目标是了解导致噪声性听力损失的分子机制。基于噪声暴露后能量耗竭引发的信号级联反应的初步研究结果，提出了瞬时能量耗竭是噪声损伤的初始关键因素的假设。瞬时能量消耗激活小的GT3途径，这反过来又导致外毛细胞中的F-肌动蛋白的破坏。瞬时能量消耗还启动了mTOR介导的细胞死亡，并阻断了mTOR信号传导途径，该途径通常充当存活功能。除了体内研究外，我们还在内耳细胞系中引入了一种新的体外能量耗尽模型，以研究噪音诱导的听力损失中疑似分子途径的特定方面。该项目的结果将导致对噪声损伤机制的新见解。此外，该项目的结果可以指导设计新的干预措施，以预防噪声引起的听力损失，从而提高个人的生活质量并降低医疗保健成本。