Altered Nitrite Reductase Activity in Diabetics (E4)

糖尿病患者亚硝酸还原酶活性改变 (E4)

• 批准号: 8294464
• 负责人: Raymond M. Esquerra
• 金额: $ 9.48万
• 依托单位: SAN FRANCISCO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8294464
• 关键词: Adult; African American; Age; American; American Indians; Area; Binding; Biochemical; Biomedical Research; Blood Glucose; Cardiovascular system; Cause of Death; Chemistry; Chronic Disease; Complications of Diabetes Mellitus; Country; Death Rate; Development Plans; Diabetes Mellitus; Diagnosis; Dissociation; Economic Burden; Electron Spin Resonance Spectroscopy; Functional disorder; General Population; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Health; Heart Diseases; Hemoglobin; Hispanics; Human; Hyperglycemia; Hypertension; Hypoxia; Kinetics; Knowledge; Ligand Binding; Link; Measures; Mentors; Methods; Molecular; Morbidity - disease rate; Nitrates; Nitric Oxide; Nitrite Reductase; Nitrites; Not Hispanic or Latino; Outcome; Physiology; Population; Prevalence; Principal Investigator; Proteins; Reaction; Research; Research Project Grants; San Francisco; Spectrum Analysis; Structure; Students; Synthesis Chemistry; Testing; Time; United States; Universities; Work; absorption; abstracting; career development; diabetic; forest; glycation; glycosylated-nitric oxide complex hemoglobin A; health disparity; insight; mortality; nanosecond; programs

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.

协作研究项目＃1 亚硝酸盐还原酶活性改变了糖尿病患者 雷蒙德·埃斯奎拉（Raymond Esquerra），首席研究员 旧金山州立大学 导师/合作者Daniel Kim-Shapiro博士 韦克森林大学 抽象的 糖尿病是一种以持续性高血糖为特征的慢性疾病，是领先的一种 美国的发病率和死亡率原因是美国的糖尿病患病率是 沿着种族界线隔离，美国印第安人，非裔美国人和西班牙裔是 患有糖尿病的非西班牙裔白人的1.8至2.2倍。许多有害 健康后果是由与血糖升高有关的并发症引起的。在 特别是心血管功能障碍是常见和致命的并发症之一 糖尿病，糖尿病成年人的心脏病死亡率大约高两到四倍 比没有糖尿病的成年人。拟议工作的长期目标是了解链接 在增加的心血管功能障碍和糖尿病之间。我们的目标是确定如何 增加的非酶糖化血红蛋白（HBA1C）破坏了正常的一氧化氮生理。 确定HB糖基化是否改变NO/HB化学是必不可少的一步 发现糖尿病与心血管功能障碍之间的基本联系。我们的 中心假设是糖化血红蛋白的一氧化氮化学被改变，并且， 因此，糖化血红蛋白水平升高会导致无生理和 糖尿病患者中与心血管相关的疾病增加。我们的理由是，通过理解 糖基化如何破坏正常的NO/HB一氧化氮化学，我们将阐明其中一种 糖尿病患者患心血管功能障碍的分子机制。这 将追求以下特定目标：1）确定糖化血红蛋白是否具有不同的亚硝酸盐 比正常成年血红蛋白还原酶活性； 2）确定糖化的血红蛋白是否具有 与正常的成年血红蛋白相比，不同的无结合和双氧化化学。 3） 确定与正常血红蛋白相比，糖化的血红蛋白是否改变了变构动力学。 结构化的职业发展计划将使Esquerra博士能够发展一个强大的独立 以及一氧化氮生理学的可持续研究计划。 Kim-Shapiro。这项研究将为独特的生物医学研究机会 在一个充满活力且迅速发展的地区的本科生和硕士学位学生不足 生物医学研究对这个国家的健康差异的主要影响。