XF24-3 Extracellular Flux Analyzer

描述（由申请人提供）：细胞能量代谢失调是许多最普遍疾病的关键特征：在2型糖尿病中，肌肉中线粒体功能减弱，并被认为在胰岛素抵抗中起关键作用;在癌症中，肿瘤细胞通常表现出线粒体呼吸减弱和糖酵解速率增加（瓦尔堡效应）;在神经变性疾病如亨廷顿病和阿尔茨海默病以及可能的其他疾病中，线粒体呼吸受损;和心血管疾病（也许所有以前的疾病），线粒体功能失调可导致活性氧物质的不完全氧化和/或积累，这会损害细胞组分并可能影响细胞凋亡。 尽管细胞线粒体和糖酵解过程的根本重要性，定量这些过程的技术一直很麻烦。用于测量线粒体脂肪酸氧化的经典方法涉及放射性标记或使用Clark氧电极，这两者都对通量、通用性和样本量要求施加了严重限制。XF 24 -3细胞外通量分析仪（Seahorse Biosciences）的可用性克服了这些局限性，并提供了以微孔板形式对细胞代谢的几个参数进行真实的定量的机制，所述参数包括糖酵解速率、脂肪酸氧化和线粒体氧化能力。加州大学洛杉矶分校的研究人员成功使用了借给我们的XF 24仪器，验证了这项技术的实用性，并为核受体、生热、癌症、脂质代谢和干细胞等领域的研究开辟了新的方向。加州大学洛杉矶分校没有其他任何类型的XF 24仪器，据我们所知，大洛杉矶地区唯一的其他仪器是在20英里外的南加州大学。本申请旨在获得XF 24 -3仪器，以确保加州大学洛杉矶分校的研究人员继续使用这项技术。 公共卫生相关性：当今美国最流行的疾病-心血管疾病、癌症、2型糖尿病、神经退行性疾病-的特征在于细胞能量代谢调节受损。细胞外通量分析仪的技术允许在真实的时间内测量少量细胞中的细胞能量途径，而不会产生放射性或有毒废物。利用这项技术进行的研究可能会更好地了解人类疾病的潜在机制，并有可能发现药物和改进治疗方法。

DESCRIPTION (provided by applicant): The dysregulation of cellular energy metabolism is a key feature of many of the most prevalent diseases: in type 2 diabetes, mitochondrial function is diminished in muscle and thought to play a key role in insulin resistance; in cancer, tumor cells often exhibit attenuated mitochondrial respiration and increased rates of glycolysis (the Warburg effect); in neurodegenerative diseases such as Huntington's disease and Alzheimer's disease and likely others, mitochondrial respiration is impaired; and in cardiovascular diseases (and perhaps all of the preceding disease as well), dysregulated mitochondrial function can lead to incomplete oxidation and/or accumulation of reactive oxygen species that cause damage to cellular components and may influence apoptosis. Despite the fundamental importance of cellular mitochondrial and glycolytic processes, techniques to quantitate these processes have been cumbersome. Classic methods for measuring mitochondrial fatty acid oxidation involve radiolabeling or the use of the Clark Oxygen Electrode, both of which impose severe limitations on the throughput, versatility, and sample size requirements. The availability of the XF24-3 Extracellular Flux Analyzer (Seahorse Biosciences) overcomes these limitations and provides a mechanism for real time quantitation in a microplate format of several parameters of cellular metabolism, including rates of glycolysis, fatty acid oxidation, and mitochondrial oxidative capacity. The successful use by investigators at UCLA of an XF24 instrument that has been on loan to us has validated the utility of this technology and opened up new directions in research in the areas of nuclear receptors, thermogenesis, cancer, lipid metabolism, and stem cells. There are no other XF24 instruments of any type at UCLA, and to our knowledge, the only other instrument in the greater Los Angeles area is at the University of Southern California, 20 miles away. This application seeks to obtain an XF24-3 instrument to ensure continued access to this technology by investigators at UCLA. PUBLIC HEALTH RELEVANCE: The most prevalent diseases in the United States today-cardiovascular diseases, cancer, type 2 diabetes, neurodegenerative diseases-are characterized by impaired regulation of cellular energy metabolism. The technology available with the Extracellular Flux Analyzer allows measurement of cellular energy pathways in small numbers of cells in real time, without the generation of radioactive or toxic waste products. Studies with this technology may lead to greater understanding of mechanisms underlying human diseases, and potentially to drug discovery and improved treatments.