XF24-3 Extracellular Flux Analyzer

描述(申请人提供)：细胞能量代谢失调是许多最常见疾病的一个关键特征：在2型糖尿病中，肌肉中的线粒体功能减弱，被认为在胰岛素抵抗中起关键作用；在癌症中，肿瘤细胞经常表现出线粒体呼吸减弱和糖酵解率增加(沃伯格效应)；在神经退行性疾病中，如亨廷顿病和阿尔茨海默病以及可能的其他疾病，线粒体呼吸受损；在心血管疾病(可能也包括所有之前的疾病)中，线粒体功能失调会导致不完全氧化和/或活性氧物种的积累，从而对细胞成分造成损害，并可能影响细胞凋亡。尽管细胞线粒体和糖酵解过程很重要，但量化这些过程的技术一直很繁琐。测量线粒体脂肪酸氧化的经典方法包括放射性标记或使用Clark氧电极，这两种方法都对吞吐量、通用性和样本量要求施加了严格的限制。XF24-3细胞外通量分析仪(海马生物科学)的推出克服了这些限制，并提供了一种以微板格式实时定量多个细胞代谢参数的机制，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地使用了借给我们的XF24仪器，验证了这项技术的实用性，并在核受体、产热、癌症、脂代谢和干细胞领域开辟了新的研究方向。加州大学洛杉矶分校没有其他任何类型的XF24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。这项申请寻求获得一台XF24-3仪器，以确保加州大学洛杉矶分校的调查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--的特点是细胞能量代谢调节受损。胞外通量分析仪提供的技术允许实时测量少量细胞中的细胞能量路径，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理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.