Fluorescent Copper Probes for Intracellular Imaging

用于细胞内成像的荧光铜探针

• 批准号: 8059099
• 负责人: CHRISTOPH J FAHRNI
• 金额: $ 10.53万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-30 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8059099
• 关键词: ATP phosphohydrolase; Affinity; Alzheimer' s Disease; Amines; Architecture; Binding; Binding Proteins; Biological; Buffers; Cell Line; Cell Membrane Permeability; Cell membrane; Cells; Cellular Structures; Chelating Agents; Collaborations; Copper; Cytoplasm; DNA; Development; Disease; Electron Transport; Equilibrium; Evaluation; Fluorescence; Fluorescent Probes; Goals; Golgi Apparatus; Health; Human; Image; Ions; Iron; Kinetics; Laboratories; Lead; Libraries; Ligands; Link; Lipids; Measurement; Membrane Proteins; Menkes Kinky Hair Syndrome; Metabolism; Metals; Molecular; Monitor; Nature; Oxidation-Reduction; Process; Production; Property; Proteins; Reaction; Research Personnel; Respiration; Secretory Vesicles; Site; Solutions; Superoxides; Techniques; Therapeutic; Thermodynamics; Time; Toxic effect; Trace Elements; Universities; Washington; base; cofactor; extracellular; fluorophore; human disease; imaging probe; in vivo; nervous system disorder; novel diagnostics; oxidative damage; programs; receptor; research study; tool; trafficking; uptake

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.

说明（申请人提供）：铜是人体必需的微量元素，对人体健康至关重要。铜的氧化还原特性需要一个复杂的管理，以避免脂质，蛋白质或DNA的氧化损伤。因此，电池必须保持一种微妙的平衡，使铜可用于催化过程，但同时避免积累到有毒水平。维持细胞内铜水平控制的详细机制和细胞结构尚不清楚。这一信息对于理解由铜失衡引起的疾病的分子机制至关重要，例如Wilson病或Menkes病，这两种疾病都是致命的。最近，包括ALS和阿尔茨海默病在内的某些神经系统疾病与铜代谢障碍有关。