Postischemic Hyperoxia and Cerebral Energy Metabolism

缺血后高氧和脑能量代谢

• 批准号: 7227770
• 负责人: ERICA M RICHARDS
• 金额: $ 3.89万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-27 至 2009-03-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7227770
• 关键词: 3-nitrotyrosine; Acetyl Coenzyme A; Adult; Affect; Animals; Area; Brain; Brain region; Canis familiaris; Cell Death; Cell Respiration; Cerebral Ischemia; Cerebrum; Citric Acid Cycle; Condition; Decarboxylation; Energy Metabolism; Enzymes; Glucose; Heart Arrest; Hippocampus (Brain); Hour; Hyperoxia; Immunoprecipitation; In Vitro; Incubated; Ischemia; Measures; Metabolic; Metabolism; Mitochondria; Modeling; Monitor; Multienzyme Complexes; NMR Spectroscopy; Oxidative Stress; Oxygen measurement, partial pressure, arterial; Period Analysis; Peroxonitrite; Physiological reperfusion; Proteins; Pyruvate; Pyruvate Dehydrogenase Complex; Pyruvates; Rate; Reaction; Reperfusion Injury; Reperfusion Therapy; Research; Resistance; Respiration; Resuscitation; Role; Sampling; Testing; Thinking; Western Blotting; beta-Hydroxybutyrate; clinically relevant; design; enzyme activity; frontal lobe; glucose metabolism; immunoreactivity; interest; neuron loss; nitration; oxidation

DESCRIPTION (provided by applicant): Our current area of interest is the effects of oxygen tension during the reperfusion period following cerebral ischemia. Specifically, our proposed research investigates the role of oxidative stress in reperfusion injury. We propose to study the difference between hyperoxic (100% O2) versus normoxic (21% O2) reperfusion following a 10 minute clinically relevant model of canine cardiac arrest and resuscitation. We hypothesize that hyperoxic resuscitation leads to increased oxidative stress which targets key metabolic enzymes, causing decreased enzyme activity and lower cellular glucose metabolism. We will utilize nuclear magnetic resonance spectroscopy to monitor metabolism of [1]-13C-glucose in postischemic animals resuscitated with either hyperoxia or normoxia. To investigate changes in metabolic enzyme activity, we will focus on the pyruvate dehydrogenase complex (PDHC), a mitochondrial enzyme that catalyzes the oxidative decarboxylation of pyruvate to acetyl-coenzyme A. We hypothesize that oxidative stress increases following ischemia/reperfusion and targets the PDHC, causing decreased enzyme activity. 3-nitrotyrosine, a marker of oxidative stress will be implemented to monitor targeting of oxidative stress to the PDHC.

描述（由申请人提供）： 我们目前感兴趣的领域是脑缺血后再灌注期间氧张力的影响。具体来说，我们提出的研究探讨氧化应激在再灌注损伤中的作用。我们建议研究高氧（100%O2）与常氧（21%O2）再灌注后10分钟的临床相关模型的犬心脏骤停和复苏之间的差异。我们假设高氧复苏导致氧化应激增加，其靶向关键代谢酶，导致酶活性降低和细胞葡萄糖代谢降低。我们将利用核磁共振光谱监测高氧或常氧复苏的缺血后动物中[1]-13 C-葡萄糖的代谢。为了研究代谢酶活性的变化，我们将关注丙酮酸脱氢酶复合物（PDHC），这是一种催化丙酮酸氧化脱羧为乙酰辅酶A的线粒体酶。我们推测，缺血/再灌注后氧化应激增加，靶向PDHC，导致酶活性降低。3-硝基酪氨酸是氧化应激的标志物，将用于监测氧化应激对PDHC的靶向作用。