Molecular Imaging Probes to Study Metal Biology

研究金属生物学的分子成像探针

• 批准号: 9119842
• 负责人: Christopher J. Chang
• 金额: $ 34.46万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-25 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9119842
• 关键词: 3T3-L1 Cells; Adipocytes; Adipose tissue; Affinity; Aging; Antioxidants; Binding; Binding Proteins; Binding Sites; Biochemical; Biochemical Genetics; Biological Assay; Biological Models; Biology; Brown Fat; Catalytic Domain; Cell model; Cell physiology; Cells; Cellular Assay; Chemicals; Copper; Copper Chelation; Cyclic AMP; Detection; Development; Diabetes Mellitus; Diet; Disease; Dyes; Environment; Enzymes; Fatty acid glycerol esters; Fluorescent Probes; Genetic; Goals; Growth and Development function; Health; Heart Diseases; Homeostasis; Human; Image; In Vitro; Label; Life; Life Style; Lipids; Lipolysis; Lung; Malignant Neoplasms; Mammalian Cell; Mediating; Metabolic Diseases; Metabolism; Metals; Methods; Modeling; Molecular; Monitor; Mutation; Neurodegenerative Disorders; Nutrient; Obesity; Organelles; Organism; Oxidation-Reduction; Oxidative Stress; PDE 3B; Pancreas; Pathway interactions; Phosphorylation; Physiological; Physiological Processes; Physiology; Play; Process; Protein Isoforms; Proteins; Regulation; Respiration; Role; Signal Pathway; Signal Transduction; Site-Directed Mutagenesis; Staging; Starvation; Stress; Supplementation; System; Techniques; Testing; Time; Tissues; Titrations; Transition Elements; Workplace; Wound Healing; X-Ray Crystallography; cell growth; cell type; copper-binding protein; genetic manipulation; hydrophilicity; imaging probe; improved; interest; lipid metabolism; molecular imaging; mutant; overexpression; oxidative damage; phosphoric diester hydrolase; research study; sensor; tool

 DESCRIPTION (provided by applicant): Copper is an essential metal nutrient that plays important roles in human health, aging, and disease. The potent redox activity of copper is required for a diverse array of physiological processes ranging from respiration to antioxidant defense to wound healing. At the same time, however, unregulated imbalances in copper homeostasis can contribute to metabolic diseases like obesity and diabetes as well as cancer, heart disease, and neurodegenerative disorders, often through aberrant oxidative stress and damage pathways. We are developing and applying new chemical tools for molecular imaging of copper in living systems with the long-term goal of understanding how and in what context this metal contributes to normal physiology as well as aging and disease. This competitive renewal application will focus on elucidating the roles of copper in lipolysis, a central process i lipid metabolism that is essential for maintaining the body's energy stores but also contributes to metabolic diseases such as obesity and diabetes. Specific aims include: developing new fluorescent copper sensors with enhanced photostability to monitor of copper dynamics and a broader range of binding affinities to access a broader range of copper pools in cells, applying these new chemical tools to probe the contributions of copper signaling to lipolysis in adipocyte cell models, and biochemical characterization of newly identified copper-protein targets that mediate lipolytic signaling pathways.

 描述（由申请人提供）：铜是一种必需的金属营养素，在人类健康、衰老和疾病中起着重要作用。铜的强氧化还原活性是从呼吸到抗氧化防御到伤口愈合的各种生理过程所必需的。然而，与此同时，铜稳态的不受调节的失衡可能导致代谢疾病，如肥胖和糖尿病以及癌症，心脏病和神经退行性疾病，通常通过异常的氧化应激和损伤途径。我们正在开发和应用新的化学工具，用于生命系统中铜的分子成像，长期目标是了解这种金属如何以及在何种情况下有助于正常生理以及衰老和疾病。这种竞争性的更新申请将集中在阐明铜在脂解中的作用，脂解是一种脂质代谢的中心过程，对维持身体的能量储存至关重要，但也有助于 代谢性疾病，如肥胖症和糖尿病。具体目标包括：开发具有增强的光稳定性的新的荧光铜传感器以监测铜动力学和更广泛的结合亲和力以访问细胞中更广泛的铜池，应用这些新的化学工具来探测铜信号传导对脂肪细胞模型中的脂解的贡献，以及新鉴定的介导脂解信号传导途径的铜蛋白靶的生物化学表征。