Altered Nitrite Reductase Activity in Diabetics

合作研究项目#1 糖尿病患者亚硝酸还原酶活性的改变 雷蒙德·埃斯奎拉，首席调查员 旧金山州立大学 Daniel Kim-Shapiro博士，导师/合作者 维克森林大学 摘要 糖尿病是一种以持续性高血糖为特征的慢性疾病，是主要的 美国的发病率和死亡率。美国的糖尿病患病率是 种族隔离，美国印第安人、非裔美国人和西班牙裔美国人 患糖尿病的可能性是非西班牙裔白人的1.8到2.2倍。许多有害的 与血糖水平升高相关的并发症会导致健康后果。在……里面 特别是，心血管功能障碍是一种常见和致命的并发症 糖尿病，糖尿病成人的心脏病死亡率大约高出两到四倍 而不是没有糖尿病的成年人。拟议工作的长期目标是了解其中的联系 心血管功能障碍增加和糖尿病之间的关系。我们的目标是确定如何 非酶糖化血红蛋白(HbA1c)的增加会扰乱正常的一氧化氮生理。 确定Hb的糖基化是否改变NO/Hb化学是 发现糖尿病和心血管功能障碍之间的潜在联系。我们的 中心假说是糖化血红蛋白的一氧化氮化学发生改变， 因此，糖化血红蛋白水平升高会导致NO生理学和 糖尿病患者心血管相关疾病增加。我们的理由是，通过理解 糖基化如何扰乱正常的NO/Hb一氧化氮化学，我们将阐明其中之一 糖尿病患者普遍存在心血管功能障碍的分子机制。这个 将追求以下具体目标：1)确定糖化血红蛋白是否具有不同的亚硝酸盐 还原酶活性高于正常成人血红蛋白；2)测定糖化血红蛋白是否有 与正常成人血红蛋白不同的NO结合和双氧合化学； 确定与正常血红蛋白相比，糖化血红蛋白是否改变了变构动力学。 一个有组织的职业发展计划将使埃斯奎拉博士能够发展出强大的独立性 和可持续的一氧化氮生理学研究计划。 金-夏皮罗。这项研究将为以下生物医学研究提供独特的机会 在一个动态和快速发展的领域中，本科生和硕士学生的代表性不足 对这个国家的健康差距有重大影响的生物医学研究。

COLLABORATIVE RESEARCH PROJECT #1 ALTERED NITRITE REDUCTASE ACTIVITY IN DIABETICS Raymond Esquerra, Principal Investigator San Francisco State University Dr. Daniel Kim-Shapiro, Mentor/Collaborator Wake Forest University Abstract Diabetes, a chronic disease characterized by persistent hyperglycemia, is one of the leading causes of morbidity and mortality in the U.S. The prevalence of diabetes in the United States is segregated along racial lines, with American Indians, African Americans, and Hispanics being 1.8 to 2.2 times more likely than non-Hispanic whites to suffer from diabetes. Many detrimental health consequences result from complications associated with elevated blood sugar levels. In particular, cardiovascular dysfunction is one of the common and deadly complications of diabetes, with heart disease death rates in diabetic adults being about two to four times higher than in adults without diabetes. The long-term goal of the proposed work is to understand the link between increased cardiovascular dysfunction and diabetes. Our objective is to determine how increased nonenzymatically glycated hemoglobin (HbA1c) disrupts normal nitric oxide physiology. Determining whether the glycation of Hb alters NO/Hb chemistry is an essential step in discovering the underlying connection between diabetes and cardiovascular dysfunction. Our central hypothesis is that the nitric oxide chemistry of glycated hemoglobin is altered and, consequently, elevated levels of glycated hemoglobin result in disrupted NO physiology and increased cardiovascular-related ailments in diabetics. Our rationale is that, by understanding how glycation disrupts normal NO/Hb nitric oxide chemistry, we will elucidate one of the molecular mechanisms underlying the cardiovascular dysfunction prevalent in diabetics. The following specific aims will be pursued: 1) determine if glycated hemoglobin has different nitrite reductase activity than normal adult hemoglobin; 2) determine if glycated hemoglobin has different NO binding and dioxygenation chemistry compared to normal adult hemoglobin; and 3) determine if glycated hemoglobin has altered allosteric kinetics compared to normal hemoglobin. A structured career development plan will allow Dr. Esquerra to develop a strong independent and sustainable research program in nitric oxide physiology under the mentored guidance of Dr. Kim-Shapiro. This research will provide unique biomedical research opportunities for underrepresented undergraduate and masters students in a dynamic and quickly evolving area of biomedical research with major implications for health disparities in this country.