Fluorescent Copper Probes for Intracellular Imaging

用于细胞内成像的荧光铜探针

• 批准号: 7037412
• 负责人: CHRISTOPH J FAHRNI
• 金额: $ 18.57万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7037412
• 关键词: X ray crystallography; bioimaging /biomedical imaging; confocal scanning microscopy; copper; electrochemistry; flow cytometry; fluorescence microscopy; fluorescent dye /probe; imaging /visualization /scanning; intracellular transport; metal metabolism

DESCRIPTION (provided by applicant): Copper is an essential trace element, which is critical to human health. The redox properties of copper require a sophisticated management to avoid oxidative damage of lipids, proteins or DNA. Therefore the cell must maintain a subtle balance, such that copper is available for catalytic processes, but at the same time avoid accumulation to toxic levels. The detailed mechanisms and cellular structures responsible for maintaining control of intracellular copper levels are not well understood. This information is critical for the understanding of the molecular mechanisms of diseases caused by copper imbalance, such as Wilson's or Menkes' disease, both of which are fatal. More recently, certain neurological disorders including ALS and Alzheimer's disease have been linked to disorders in copper metabolism. One of the central hypotheses of the copper regulatory machinery suggests the presence of intracellular storage or buffer sites as a defense against deficiency, but also to protect the cell from abnormally high concentrations of copper. Golgi secretory vesicles which contain a copper ATPase membrane protein might function as intracellular compartments for copper storage. Fluorescence probes, which can permeate the plasma membrane are powerful tools for the study of intracellular metal ion distributions, yet rigorous analytical techniques for sensitive in vivo measurements of intracellular copper levels are completely lacking. The goal of the proposed project is the development of a copper specific fluorescent probe, which would not only allow to monitor vesicular labile copper concentrations, but would also provide information about the subcellular distribution in cell lines with disorders in copper metabolism. In a larger context a copper specific fluorescent probe will be of great importance for the long-term development of novel diagnostic and therapeutic tools for copper related human diseases.

描述（由申请人提供）：铜是必不可少的痕量元素，对人类健康至关重要。铜的氧化还原特性需要复杂的管理，以避免脂质，蛋白质或DNA的氧化损伤。因此，细胞必须保持微妙的平衡，使铜可用于催化过程，但同时避免积累到有毒水平。尚不清楚负责控制细胞内铜水平的详细机制和细胞结构。这些信息对于理解由铜不平衡引起的疾病的分子机制至关重要，例如威尔逊或梅克斯氏病，两者都是致命的。最近，某些包括ALS和阿尔茨海默氏病在内的神经系统疾病与铜代谢中的疾病有关。 铜调节机械的中央假设之一表明，存在细胞内存储或缓冲位点作为防御缺乏的防御，但也可以保护细胞免受异常高浓度的铜的侵害。包含铜ATPase膜蛋白的高尔基分泌囊泡可能是铜存储的细胞内室。可以渗透质膜的荧光探针是研究细胞内金属离子分布的强大工具，但是对于敏感的细胞内铜水平的敏感分析技术，完全缺乏敏感的分析技术。拟议项目的目的是开发铜线特异性荧光探针，该探针不仅允许监测囊泡不稳定的铜浓度，而且还将提供有关在铜代谢中具有疾病的细胞系中细胞系中细胞分布的信息。在较大的情况下，铜线特异性荧光探针对于长期开发用于铜相关的人类疾病的新型诊断和治疗工具将非常重要。