Noise-induced acute hair cell Death

噪音引起的急性毛细胞死亡

• 批准号: 8663588
• 负责人: BO HUA HU
• 金额: $ 38.36万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8663588
• 关键词: Acoustic Trauma; Acquired Deafness; Actins; Acute; Address; Adhesions; Age; Apoptosis; Apoptotic; Biological; Cell Adhesion; Cell Adhesion Molecules; Cell Death; Cell Membrane Permeability; Cell membrane; Cells; Clinical; Cytoskeletal Modeling; Cytoskeleton; Data; Development; E-Cadherin; Event; Exposure to; Functional disorder; Generations; Genes; Goals; Hair Cells; Homeostasis; Interruption; Knowledge; Labyrinth; Lead; Link; Maintenance; Mechanical Stress; Mechanics; Mediating; Membrane; Military Personnel; Molecular; Molecular Genetics; Necrosis; Noise; Noise-Induced Hearing Loss; Pathogenesis; Pathology; Phase; Physiology; Play; Process; Protein Analysis; Proteins; Regulation; Research; Role; Sensory; Signal Transduction; Site; Structure; Testing; Tracer; Trauma; Work; base; cofactor; depolymerization; disability; high throughput technology; innovation; insight; novel; novel therapeutics; repaired; research study; response; surfactant

DESCRIPTION (provided by applicant): The plasma membrane of the cell plays an essential role in the maintenance of cellular homeostasis. It is also the first site in transferring a mechanical force into the hair cell. While strong evidence has implicated membrane disruption as an early event of hair cell degeneration in noise-induced cochlear trauma, it is unclear how such damage contributes to the pathogenesis of acute hair cell death. Our long-term goal is to better understand the biological and molecular mechanisms of noise-induced hearing loss. The objective of this research is to determine the role of membrane disruption in the generation of acute hair cell death. The central hypothesis for the proposed research is that membrane dysfunction is involved in the regulation of acute hair cell apoptosis. We plan to test our central hypothesis by examining two essential functions of the plasma membrane, membrane barrier and membrane adhesion. Specifically, the following three aims will be addressed: (1) to determine the role of membrane permeabilization in the regulation of acute hair cell death and evaluate the effect of a membrane repair strategy on the hair cell's response to mechanical stress, (2) to determine the effect of the disruption of membrane adhesion on the cytoskeletal structure of apoptotic hair cells, and (3) to identify the apoptosis-related molecules that are involved in the generation of acute cochlear damage. Our contribution here is expected to increase understanding of the regulatory mechanism of acute hair cell apoptosis. This contribution is significant because the new insights into acute membrane dysfunction fill the knowledge gap between direct mechanical stress and subsequent signal transduction leading to cell death. Importantly, controlling the membrane events of apoptosis may lead to the development of novel pharmacological strategies for suppression of acute hair cell death.

描述(由申请人提供)：细胞的质膜在维持细胞内稳态方面起着重要的作用。它也是第一个将机械力传递到毛细胞中的场所。虽然有强有力的证据表明，膜破坏是噪声性耳蜗损伤毛细胞退化的早期事件，但这种损伤如何参与急性毛细胞死亡的发病机制尚不清楚。我们的长期目标是更好地了解噪声性听力损失的生物学和分子机制。这项研究的目的是确定膜破裂在急性毛细胞死亡发生中的作用。这项研究的中心假设是，膜功能障碍参与了急性毛细胞凋亡的调节。我们计划通过检查质膜的两个基本功能--膜屏障和膜黏附来检验我们的中心假设。具体地说，将涉及以下三个目标：(1)确定膜通透性在调节急性毛细胞死亡中的作用，并评价膜修复策略对毛细胞对机械应力的反应的影响；(2)确定膜黏附破坏对凋亡毛细胞细胞骨架结构的影响；(3)确定参与急性耳蜗病发生的凋亡相关分子。我们的贡献有望加深对急性毛细胞凋亡调控机制的理解。这一贡献意义重大，因为对急性膜功能障碍的新见解填补了直接机械应激与随后导致细胞死亡的信号转导之间的知识空白。重要的是，控制细胞凋亡的膜事件可能导致抑制急性毛细胞死亡的新的药理策略的发展。