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障碍的主要原因，也是工业化国家最常见的与工作有关的残疾之一。本研究的长期目标是了解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的初步结果，提出了瞬时能量耗尽是噪声损伤的初始关键因素的假说。短暂的能量耗竭激活了小的GTP酶通路，进而导致外毛细胞中F-肌动蛋白的破坏。短暂的能量耗竭也会启动线粒体介导的细胞死亡，并阻断通常作为生存功能的mTOR信号通路。除了体内研究，我们正在引入一种新的内耳细胞系能量耗竭的体外模型，以研究可能导致噪声导致听力损失的分子通路的特定方面。该项目的结果将为噪声创伤的机制带来新的见解。此外，该项目的结果可能会指导设计新的干预措施，以预防噪声引起的听力损失，有利于个人的生活质量，并降低医疗保健成本。