Molecular Mechanisms in Noise-Induced Hearing Loss

噪声性听力损失的分子机制

• 批准号: 8128221
• 负责人: Su-Hua Sha
• 金额: $ 33.92万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 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/8128221
• 关键词: F-Actin; Molecular; Noise-Induced Hearing Loss; Preventive Intervention; in vitro Model; in vivo; mTOR Signaling Pathway

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相关的残疾之一。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损耗引发的信号级联的令人兴奋的初步结果，提出了假设：瞬时能量损耗是噪声创伤的最初关键因素。瞬时能量消耗会激活小的 GTP 酶途径，进而导致外毛细胞中 F-肌动蛋白的破坏。瞬时能量消耗还会引发线粒体介导的细胞死亡，并阻断通常发挥生存功能的 mTOR 信号通路。除了体内研究之外，我们还引入了一种新型的内耳细胞系能量消耗体外模型，以研究疑似噪声引起的听力损失的分子途径的特定方面。该项目的结果将带来对噪音创伤机制的新​​见解。此外，该项目的结果可能会指导设计新颖的干预措施，以预防噪音引起的听力损失，从而有利于个人的生活质量并降低医疗保健成本。