XAS OF BIOINORGANIC SYSTEMS

生物无机系统的 XAS

• 批准号: 7598150
• 负责人: PETER A LAY
• 金额: $ 0.28万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598150
• 关键词: Area; Binding; Cardiac Myocytes; Cardiovascular Diseases; Cells; Complement; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Environment; Enzymes; Freezing; Funding; Grant; Heme; Hemoglobin; Human; Hydrogen Peroxide; Institution; Insulin; Lead; Lung; Metabolic Biotransformation; Monitor; Muscle Cells; Myoglobin; Phosphoric Monoester Hydrolases; Precipitation; Prevention; Process; Protein Binding; Proteins; Raman Spectrum Analysis; Reaction; Research; Research Personnel; Resources; Source; Staging; Structure; System; Techniques; Thinking; United States National Institutes of Health; Work; adduct; chromium hexavalent ion; diabetic; dietary supplements; in vivo; mutant; oxidation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Changes in the heme environment when the a-hemoglobin stabilizing protein (AHSP) binds to a-hemoglobin (a-Hb), which we have studied by Raman spectroscopy, will be monitored by Fe K-edge XAFS. Such binding is important in prevention of toxic heme precipitation from unstable oxy-a-Hb, but all crystal structures of AHSP:oxy-a-Hb complexes contain mutant Hb and it is not clear whether the structures are the same as with the wild type because they have different reactivities. Fe K-edge XAFS will also be used to study the reactions of myoglobin with H2O2 in cardiac myocytes. Such processes are thought to lead ultimately to cardiovascular disease and XAS will be recorded on snap frozen cell pellets of the myocytes (using previously developed techniques) that are untreated or H2O2-treated and changes in the Mb XAS will be monitored. Cr K-edge XAFS will be recorded on Cr(VI) adducts of phosphatase enzymes (for which there are no structural data), since we have recently shown that anti-diabetic effects of commonly used Cr(III) dietary supplements are likely to be exerted by in-vivo enzymatic oxidation of the Cr(III) dietary supplements to carcinogenic Cr(VI), followed increased insulin activity due to potent Cr(VI) inhibition of phosphatase enzymes We also intend to study the very early stages of the biotransformations of Cr(VI) in human lung cells to complement our recent work in the area.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们通过拉曼光谱研究了α-血红蛋白稳定蛋白（AHSP）与α-血红蛋白（a-Hb）结合时血红素环境的变化，将通过Fe K边缘XAFS进行监测。这种结合对于防止不稳定的 oxy-a-Hb 产生有毒血红素沉淀非常重要，但 AHSP:oxy-a-Hb 复合物的所有晶体结构都含有突变型 Hb，并且尚不清楚这些结构是否与野生型相同因为它们有不同的反应性。 Fe K-edge XAFS 还将用于研究心肌细胞中肌红蛋白与 H2O2 的反应。 这种过程被认为最终会导致心血管疾病，XAS 将记录在未经处理或 H2O2 处理的心肌细胞速冻细胞沉淀上（使用先前开发的技术），并监测 Mb XAS 的变化。 Cr K-edge XAFS 将记录在磷酸酶的 Cr(VI) 加合物上（没有结构数据），因为我们最近表明常用 Cr(III) 膳食补充剂的抗糖尿病作用可能是Cr(III) 膳食补充剂体内酶促氧化为致癌 Cr(VI)，随后由于 Cr(VI) 对磷酸酶的有效抑制而增加了胰岛素活性。我们还打算研究早期阶段Cr(VI) 在人肺细胞中的生物转化，以补充我们最近在该领域的工作。