Consequences of Lipid Restructuring During Temperature Variation on the Susceptibility of Biological Membranes to Lipid Peroxidation

温度变化期间脂质重组对生物膜脂质过氧化敏感性的影响

• 批准号: 0842624
• 负责人: Elizabeth Crockett
• 金额: $ 48.46万
• 依托单位: Ohio University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-15 至 2014-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0842624&HistoricalAwards=false
• 关键词: Consequences; Lipid; Restructuring; During; Temperature

Life in the presence of oxygen involves the regular production of reactive oxygen species (including free radicals) and other highly reactive molecules. Some of these compounds can initiate lipid peroxidation (LPO), a series of reactions that can significantly alter the chemical, physical, and functional properties of biological membranes. Although LPO may damage cells, a certain level appears necessary for a variety of cellular processes. Poikilothermic animals (i.e., animals that live at a variety of body temperatures) represent the vast majority of animals that live on earth. In order to keep membranes at or near an optimal fluidity, poikilotherms alter the chemical compositions of their biological membranes with changes in body temperature. At low temperatures, poikilotherms have membranes particularly rich in the phospholipid phosphatidylethanolamine and omega-3 polyunsaturated fatty acids. In addition, their cells often have higher contents of energy-producing mitochondria, the primary source of reaction oxygen species. These changes could make animals at cold temperatures more vulnerable to LPO than their warm-bodied counterparts. At the same time, low temperature slows rates of LPO and production of reactive oxygen species. Using a fish model (the striped bass, Morone saxatilis), this work will test the central hypothesis that membrane susceptibility to LPO is maintained over a range of body temperatures. Other objectives include quantification of LPO products and antioxidant defenses. Recently developed fluorescent probes and chromatographic techniques will be used to address hypotheses. LPO is intensively studied in biomedicine and aging biology, yet the significance of membrane peroxidation, within the contexts of temperature physiology, has yet to be elucidated. Studies aimed at determining susceptibilities to LPO are necessary to clarify how poikilotherms avoid potentially damaging peroxidation of biological membranes. This research will contribute to a mechanistic understanding of biochemical factors that make life possible over a range of temperatures. The project will incorporate mentorship and training of graduate, undergraduate, and high school students (including research at a marine laboratory), collaboration with a faculty member from a predominantly undergraduate institution, consultation with an established researcher in the field of biomedical research, and outreach designed to educate children about how organisms adapt to life at different temperatures.

在氧气存在下的生命涉及活性氧（包括自由基）和其他高活性分子的定期生产。 这些化合物中的一些可以引发脂质过氧化（LPO），这是一系列可以显着改变生物膜的化学，物理和功能特性的反应。 虽然LPO可能损害细胞，但一定水平的LPO似乎是各种细胞过程所必需的。 变温动物（即，生活在各种体温下的动物）代表了生活在地球上的绝大多数动物。 为了保持膜处于或接近最佳流动性，变温动物会随着体温的变化改变其生物膜的化学成分。 在低温下，变温动物的膜特别富含磷脂酰乙醇胺和ω-3多不饱和脂肪酸。 此外，它们的细胞通常具有较高含量的能量产生线粒体，这是反应氧的主要来源。 这些变化可能使动物在寒冷的温度下比温暖的身体更容易受到LPO的影响。 同时，低温降低了LPO和活性氧的产生速率。 使用鱼类模型（条纹鲈鱼，Morone saxatilis），这项工作将测试的核心假设，即膜的敏感性LPO保持在一个体温范围内。 其他目标包括定量LPO产品和抗氧化防御。 最近开发的荧光探针和色谱技术将用于解决假设。 LPO在生物医学和衰老生物学中被广泛研究，但在温度生理学背景下，膜过氧化的意义尚未阐明。 旨在确定对LPO的亲油性的研究对于阐明变温动物如何避免生物膜的潜在破坏性过氧化是必要的。 这项研究将有助于对生物化学因素的机械理解，这些因素使生命在一定温度范围内成为可能。该项目将包括对研究生、本科生和高中生的指导和培训（包括在海洋实验室的研究），与一个以本科为主的机构的一名教员合作，与生物医学研究领域的一名知名研究人员协商，以及旨在教育儿童生物体如何适应不同温度下的生活的外联活动。