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

有氧气存在的生命涉及到活性氧（包括自由基）和其他高活性分子的定期生产。其中一些化合物可以引发脂质过氧化（LPO），这一系列反应可以显著改变生物膜的化学、物理和功能特性。虽然LPO可能损害细胞，但一定水平的LPO似乎是多种细胞过程所必需的。变温动物（即生活在不同体温下的动物）代表了地球上绝大多数的动物。为了使膜保持或接近最佳的流动性，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、磷脂酰乙醇胺和omega-3多不饱和脂肪酸。此外，它们的细胞通常含有更高的能量产生线粒体，这是反应氧的主要来源。这些变化可能使低温动物比温暖动物更容易受到LPO的伤害。同时，低温减慢了LPO的速率和活性氧的产生。利用鱼类模型（斑纹鲈鱼），这项工作将验证膜对LPO的敏感性在一定体温范围内保持不变的中心假设。其他目标包括定量的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得到了广泛的研究，但在温度生理学的背景下，膜过氧化的意义尚未得到阐明。研究旨在确定对LPO的敏感性是必要的，以阐明变温动物如何避免潜在的破坏性生物膜过氧化。这项研究将有助于从机制上理解使生命在一定温度范围内成为可能的生化因素。该项目将包括对研究生、本科生和高中生的指导和培训（包括在海洋实验室进行研究），与一所以本科生为主的机构的教员合作，向生物医学研究领域的知名研究人员咨询，以及旨在教育儿童生物如何适应不同温度下的生活的外展活动。

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.