Determination of Metabolic State of Hair Cell Mitochondria by FLIM

FLIM 测定毛细胞线粒体的代谢状态

• 批准号: 7470876
• 负责人: RICHARD John HALLWORTH
• 金额: $ 21.22万
• 依托单位: CREIGHTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-03 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7470876
• 关键词: Acoustic Trauma; Acoustics; Adenine; Age; Aging; Animals; Apical; Apoptosis; Area; Auditory; Binding; Bioenergetics; Caspase; Cell Death; Cell Respiration; Cells; Cessation of life; Cochlea; Condition; Consumption; Coupled; Cytoplasm; Deterioration; Development; Dinucleoside Phosphates; Disease; Etiology; Event; Exhibits; Fluorescence; Frequencies; Hair Cells; Health; Image; Imaging Techniques; Inborn Genetic Diseases; Individual; Inner Hair Cells; Isoenzymes; Life; Location; Measures; Mechanical Stimulation; Mediating; Metabolic; Metabolism; Methods; Mitochondria; Modality; Molecular; Molecular Genetics; Movement; Mus; NADH; Nature; Neurosciences; Nicotinamide adenine dinucleotide; Nicotine; Noise; Organ of Corti; Outer Hair Cells; Oxidative Phosphorylation; Oxidative Stress; Pathogenesis; Physiology; Population; Preparation; Public Health; Rate; Respiratory Chain; Sensorineural Hearing Loss; Stress; Stria Vascularis; Testing; Time; Trauma; base; cell type; coping; deafness; disability; improved; research study; response; theories

DESCRIPTION (provided by applicant): The proximate cause of sensorineural hearing loss is the death of irreplaceable cochlear hair cells, but the underlying basis of the selective vulnerability of hair cells to a variety of traumas and diseases is unknown. A prominent theory is the inability of hair cells to cope with metabolic demands, which would thereby trigger mitochondrial caspase- mediated apoptosis, but evidence for this theory is indirect. As we here show, it is now possible to assess the state of oxidative metabolism in hair cell mitochondria from the emissions of reduced nicotine adenine dinucleotide, an intermediate in oxidative phosphorylation. This proposal seeks support to develop application of this imaging technique to the problem of metabolic imaging in hair cells. We further request support to test the hypothesis that known differences in the vulnerability of cochlear outer hair cells compared to inner hair cells, and of basal turn hair cells compared to apical turn hair cells, correlate with differences in metabolic responses in the respective hair cell populations. The proposed development and experiments, we believe, represent the first steps in a new era of quantitation of oxidative metabolism in living hair cells that will greatly add to our understanding of many aspects of normative and pathological cochlear physiology. PUBLIC HEALTH RELEVANCE Narrative Deafness is a major cause of disability in the population and is likely to increase in significance as the population ages. The major form of deafness, called sensorineural, involves the loss of irreplaceable hair cells, which may be due to an inability to cope with metabolic challenges. Our project is to evaluate a new method of quantifying the metabolic state of living hair cells.

描述（由申请人提供）：感官听力损失的近端原因是不可替代的耳蜗毛细胞的死亡，但是毛细胞对多种创伤和疾病的选择性脆弱性的基础是未知的。一个突出的理论是毛细胞无法应付代谢需求，从而触发线粒体caspase介导的细胞凋亡，但是该理论的证据是间接的。正如我们在这里所示，现在可以通过减少尼古丁腺嘌呤二核苷酸的排放来评估毛细胞线粒体中氧化代谢的状态，这是一种氧化磷酸化的中间体。该提案寻求支持将这种成像技术应用于毛细胞中代谢成像问题的应用。我们进一步要求支持以下假设：与内毛细胞相比，与顶毛毛细胞相比，与内毛细胞相比，耳蜗外毛细胞脆弱性的已知差异与毛细胞相比，与各自毛细胞群体中代谢反应的差异相关。我们认为，拟议的开发和实验代表了活毛细胞中氧化代谢的新时代的第一步，这将极大地增加了我们对规范和病理人工耳蜗生理学许多方面的理解。公共卫生相关性叙事聋哑是造成人口残疾的主要原因，随着人口年龄的增长，意义可能会增加。耳聋的主要形式称为感觉神经性，涉及不可替代的毛细胞的丧失，这可能是由于无法应对代谢挑战。我们的项目是评估一种量化活毛细胞代谢状态的新方法。