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.
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.
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