FAK mediates noise-induced loss of auditory hair cell function and survival

FAK 介导噪声引起的听毛细胞功能和存活的丧失

基本信息

批准号：
10527266
负责人：
ALFRED L NUTTALL
金额：
$ 23.1万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-03 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10527266
关键词：
Auditory Auditory Threshold Auditory system Biochemical Blood flow Cell Death Cell Survival Cell physiology Cells Cessation of life Dynamin Environment Focal Adhesion Kinase 1 Functional disorder Goals Hair Cells Health Hearing In Vitro Integrin Signaling Pathway Integrins Knockout Mice Label Labyrinth Lateral Lead Loudness LoxP-flanked allele Mammals Measurement Mediating Mediator of activation protein Methods Mitochondria Molecular Molecular Conformation Morphology Mus Natural regeneration Nature Noise Noise-Induced Hearing Loss Organ of Corti Organelles Outer Hair Cells Pathway interactions Phosphorylation Phosphotransferases Physiology Prevention Process Production Protein Tyrosine Kinase Proteins Reactive Oxygen Species Role Sensory Signal Transduction Stress Stretching Testing Time Transgenic Mice Work base biological adaptation to stress cell type environmental change fluorescence imaging hearing impairment high resolution imaging in vivo innovation mitochondrial dysfunction mouse model new therapeutic target novel preservation programs sound success

项目摘要

Project Summary Mitochondrial dysfunction has long been recognized as an underlying mechanism of noise-induced loss of hearing sensitivity (NIHL). However, the initiating processes that lead to this dysfunction is poorly understood. This proposal is founded upon new and important findings involving changes in mitochondrial dynamics in outer hair cells after loud sound exposure. Mitochondria are highly dynamic organelles that constantly undergo fission and fusion to adapt to changes in the cellular environment, and it is becoming increasingly clear that mitochondrial morphology is directly related to mitochondrial function and, therefore, the health and survival of the cell. The studies proposed here will examine a potential integrin signaling pathway for induction of mitochondrial fission activity. Specifically, we will investigate the role of FAK as a mediator of noise-induced overstimulation of OHCs leading to cell death and loss of hearing sensitivity.

项目摘要线粒体功能障碍长期以来一直被认为是噪声引起的损失的基本机制听力灵敏度（NIHL）。但是，导致这种功能障碍的启动过程知之甚少。该提案建立在新的重要发现上，涉及外部线粒体动力学的变化毛细胞大声曝光后。线粒体是高度动态的细胞器，不断发生裂变融合以适应细胞环境的变化，并且越来越清楚线粒体形态与线粒体功能直接相关，因此细胞。这里提出的研究将检查潜在的整合素信号传导途径，以诱导线粒体裂变活性。具体而言，我们将研究FAK作为噪声诱导的中介者的作用 OHC的过度刺激导致细胞死亡和听力敏感性丧失。