NMR STUDIES OF CELLULAR METABOLISM

细胞代谢的核磁共振研究

• 批准号: 6290004
• 负责人: Robert E London
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6290004
• 关键词: acetone; cellular respiration; cytochrome P450; enzyme activity; fluorine; glutathione; glycerol kinase; halogenation; intracellular; laboratory rat; nonsteroidal antiinflammatory agent; nuclear magnetic resonance spectroscopy; phenols; pyruvate kinase; quinones

The development of an artificial liver represents a long standing goal of toxicology as well as medicine. Attempts to utilize various bioreactor models have had only moderate success, with systems being relatively short lived and showing poor expression of drug metabolizing enzymes such as cytochrome P450. However, recent advances in the development of stem cell technology have brought this goal considerably closer to reality. We have recently been working with Prof. Lola Reid and Dr. Jeffrey Macdonald at the University of North Carolina to utilize NMR as a non-invasive tool for assessing various metabolic and flow parameters in several hepatic bioreactor model systems. Dr. Reids group has recently developed an antibody screening method that will be used to negatively sort human hepatic progenitors by fluorescent activated cell sorting, allowing enrichment of hepatic progenitor populations. We also recently have been able to demonstrate the feasibility of NMR monitoring of fluorinated xenobiotic metabolism, as well as a number of other metabolic parameters in a commercially available bioreactor. Preliminary NMR studies utilizing a miniature bioreactor that mimics a human liver lobule have also been performed.We have also recently used NMR spectroscopy to understand the physiology and toxicology of borate. These studies involve the analysis of the ternary complex formed from borate, serine, and the enzyme gamma glutamyl transpeptidase. - artificial liver; bioreactor; NMR; propionate; bacterial cell wall; borate; fluorinated xenobiotics

人造肝的发展代表了毒理学和医学的长期目标。利用各种生物反应器模型的尝试只有中等的成功，系统的寿命相对较短，并且显示出药物代谢酶（例如细胞色素p450）的表达不佳。但是，干细胞技术发展的最新进展使这一目标更接近现实。最近，我们一直在北卡罗来纳大学与Lola Reid教授和Jeffrey MacDonald博士合作，利用NMR作为一种非侵入性工具，用于评估几种肝生物反应器模型系统中的各种代谢和流程参数。 Reids Group博士最近开发了一种抗体筛选方法，该方法将通过荧光激活的细胞分选来负面分类人肝祖细胞，从而富集肝祖细胞种群。最近，我们还能够证明NMR监测氟化异生物代谢的可行性，以及在市售生物反应器中的许多其他代谢参数。使用微型生物反应器的初步NMR研究也已经进行了模仿人肝小叶。我们最近还使用NMR光谱来了解硼酸盐的生理学和毒理学。这些研究涉及对由硼酸盐，丝氨酸和酶gamma谷氨酸转肽酶形成的三元复合物的分析。 - 人造肝；生物反应器； NMR;丙酸细菌细胞壁；硼酸盐；氟化生物生物