XAS OF METALS AND METALLOIDS IN INTRACELLULAR COMPARTMENTS

细胞内金属和准金属的 XAS

• 批准号: 7597951
• 负责人: HELEN NICHOL
• 金额: $ 0.22万
• 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/7597951
• 关键词: Address; Animal Model; Animal Organ; Cell Nucleus; Cells; Chelating Agents; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Copper; Custom; Development; Disease; Drosophila genus; Fingerprint; Funding; Genes; Goals; Grant; Homologous Gene; Human; Image; In Situ; Institution; Iron; Iron Overload; Lead; Localized; Metabolic Diseases; Metals; Mitochondria; Mutate; Neurologic; Pathway interactions; Positioning Attribute; Proteins; Research; Research Personnel; Resources; Roentgen Rays; Selenite; Selenium; Source; Spatial Distribution; Spectrum Analysis; Sulfur; System; Techniques; United States National Institutes of Health; Water; Yeasts; absorption; bioaccumulation; link protein; selenate

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. The nucleus, mitochondria and vacuolar system are cellular compartments containing subsets of proteins that carry out specific functions. We propose to determine the form of metals and metalloids localized to compartments using two systems. First, we propose to determine the form of accumulated iron in isolated mitochondria. Mitochondrial iron overload is a common feature of several neurological and metabolic diseases. Currently, it is assumed that all excess mitochondrial iron is the same but there is no structural evidence to support this view. The form of iron that accumulates may depend on the pathway that is disrupted. To address this issue we will utilize the well-characterized yeast iron/sulfur cluster pathway. Using XAS, we propose to characterize the mitochondrial iron that accumulates when specific proteins, linked to iron/sulfur cluster assembly, are mutated. We will collect iron K-edges for fingerprinting and examine both the near edge and the EXAFS when appropriate. Since some of these yeast genes have human homologues that cause specific diseases, a definitive characterization of the species present could lead to the development of 'custom iron chelators'. Secondly, we propose to determine copper and selenium species in whole animals and organs that are known to sequester these compounds. X-ray absorption spectroscopy imaging is a relatively new technique that has been used to interrogate the spatial distribution of different chemical species in situ. We propose to extend this technique to two animal models, the compartmentalization of copper in the cuprophilic cells of the fruit fly and selenium bioaccumulation in the water boatman. Both Se and Cu XAS spectra, have a difference of about 7eV between the near edge maximal peak positions of selenite vs selenate and cupric vs cuprous compounds. This shift provides ample contrast for chemically selective XAS imaging. Our long-term goal is to apply XAS imaging to mammalian systems.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞核、线粒体和空泡系统是包含执行特定功能的蛋白质子集的细胞区室。我们建议使用两个系统来确定金属和准金属的形式。首先，我们建议确定在分离的线粒体中积累的铁的形式。线粒体铁超载是几种神经和代谢疾病的共同特征。目前，假设所有多余的线粒体铁都是相同的，但没有结构证据支持这一观点。铁的积累形式可能取决于被破坏的途径。为了解决这个问题，我们将利用充分表征的酵母铁/硫簇途径。我们建议使用XAS来表征当与铁/硫簇组装相关的特定蛋白质发生突变时积累的线粒体铁。我们将收集铁K边用于指纹识别，并在适当的时候检查近边和EXAFS。由于这些酵母基因中的一些具有引起特定疾病的人类同源物，因此对存在的物种的明确表征可能导致“定制铁螯合剂”的开发。其次，我们建议确定整个动物和已知可螯合这些化合物的器官中的铜和硒物种。X射线吸收光谱成像是一种相对较新的技术，已被用来询问不同的化学物种在原位的空间分布。我们建议将这种技术扩展到两个动物模型，铜的区室化的嗜铜细胞的果蝇和硒的生物积累的水船夫。Se和Cu的XAS谱在亚硒酸盐与硒酸盐和二价铜与二价铜化合物的近边最大峰位置之间有约7 eV的差异。这种偏移为化学选择性XAS成像提供了充足的对比度。我们的长期目标是将XAS成像应用于哺乳动物系统。