Selenium Antioxidant Mechanisms: Metal Binding vs. Reactive Oxygen Species Scavenging

由于这个奖项从生命过程的化学计划，博士朱莉娅L。来自克莱姆森大学的Brumaghim将研究硒抗氧化活性的分子决定因素。在氧化应激条件下，铁和铜产生的羟基自由基会导致DNA损伤和细胞死亡，控制这种损伤是一个重要的细胞过程。 硒抗氧化剂治疗以防止DNA损伤是一个活跃的研究领域，多项研究正在产生有希望的，但往往是矛盾的结果，强调需要进一步研究硒抗氧化活性的基本机制。 Brumaghim博士最近确定硒抗氧化剂通过结合金属离子，防止产生或释放有害的羟基自由基来防止氧化DNA损伤。 新项目将研究金属配位作为一种新的硒抗氧化机制，并将其与更传统的硒抗氧化活性机制（如谷胱甘肽过氧化物酶活性和活性氧清除）进行比较。 Brumaghim博士和她的学生将合成硒抗氧化剂与Fe 2+和Cu+离子的配位络合物，以确定金属结合如何导致抗氧化活性，并量化硒抗氧化剂抑制铜，铁和过氧亚硝酸盐介导的DNA损伤的能力。本研究首次将硒的抗氧化机制从基础配位化学到DNA损伤研究进行了系统比较，其研究成果将拓展配位化学、氧化损伤和硒生物化学领域。 除了这项研究所代表的科学进步外，进行这些研究将促进研究生和本科生在与无机和生物化学不断发展的领域相关的各种技术方面的培训。 它还将建立或扩大Brumaghim博士和教授之间的研究伙伴关系。克雷格贝斯（旧自治领大学），帕梅拉里格斯-格拉斯科（查尔斯顿学院），和R。肯尼斯·马库斯（克莱姆森大学）。 研究成果将通过科学出版物和在科学会议和大学举办的研讨会以及通过面向公众的研讨会广泛传播。Brumaghim博士还将与克莱姆森大学的南卡罗来纳州DNA学习中心合作，举办一个关于抗氧化剂及其预防DNA损伤能力的夏季教师培训讲习班。该研讨会将为高中教师提供实践活动和关于抗氧化剂流行话题的最新知识。

As a result of this award from the Chemistry of Life Processes Program, Dr. Julia L. Brumaghim, from Clemson University, will study the molecular determinants of selenium antioxidant activity. Iron and copper-generated hydroxyl radical causes DNA damage and cell death under oxidative stress conditions, and controlling this damage is a vital cellular process. Selenium antioxidant treatment to prevent DNA damage is an active area of research, and multiple studies are yielding promising but often contradictory results that highlight the need for additional research into the fundamental mechanisms of selenium antioxidant activity. Dr. Brumaghim has recently established that selenium antioxidants prevent oxidative DNA damage by binding metal ions, preventing generation or release of damaging hydroxyl radical. The new project will investigate metal coordination as a novel selenium antioxidant mechanism and compare it to more traditional mechanisms of selenium antioxidant activity, such as glutathione peroxidase activity and reactive oxygen species scavenging. For this work, Dr. Brumaghim and her students will synthesize coordination complexes of selenium antioxidants with Fe2+ and Cu+ ions to determine how metal binding results in antioxidant activity, and quantify the ability of selenium antioxidants to inhibit copper-, iron-, and peroxynitrite-mediated DNA damage. This research represents the first systematic comparison of selenium antioxidant mechanisms from basic coordination chemistry to DNA damage studies, and the results of this research will extend the fields of coordination chemistry, oxidative damage, and selenium biochemistry. In addition to the scientific advances this research represents, performing these studies will promote graduate and undergraduate student training in a broad variety of techniques related to the growing fields of inorganic and biological chemistry. It will also establish or expand research partnerships between Dr. Brumaghim and Profs. Craig Bayse (Old Dominion University), Pamela Riggs-Gelasco (College of Charleston), and R. Kenneth Marcus (Clemson University). Research results will be disseminated broadly through scientific publications and seminars at scientific conferences and universities, as well as through seminars for the general public. Dr. Brumaghim will also develop a summer teacher-training workshop on antioxidants and their ability to prevent DNA damage in conjunction with the South Carolina DNA Learning Center at Clemson University. This workshop will provide high school teachers with hands-on activities and state-of-the-art knowledge about the popular topic of antioxidants.