Molecular Imaging Probes to Study Redox Biology

用于研究氧化还原生物学的分子成像探针

• 批准号: 8471116
• 负责人: Christopher J. Chang
• 金额: $ 29.73万
• 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 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8471116
• 关键词: Aging; Biology; Bioluminescence; Brain; Breathing; Cardiovascular Diseases; Cell model; Cells; Cellular Stress; Chemicals; Chemistry; Color; Complex; Consumption; Cultured Cells; Data; Detection; Disease; Event; Fluorescence; Fluorescent Probes; Goals; Growth Factor; Health; Heart Diseases; Human; Hydrogen Peroxide; Image; Label; Lead; Life; Lipids; Locales; Malignant Neoplasms; Mediating; Methods; Modality; Modeling; Molecular; Monitor; Neuraxis; Neurodegenerative Disorders; Neurons; Neurotransmitters; Nitric Oxide; Nucleic Acids; Organ; Organism; Oxidation-Reduction; Oxidative Stress; Oxygen; Pain; Pathway interactions; Physiological; Physiology; Play; Process; Production; Proteins; Reactive Oxygen Species; Reagent; Reporter; Resolution; Role; Sampling; Signal Transduction; Site; Source; Specificity; Specimen; Stress; Thick; Time; Tissues; Whole Organism; Wound Healing; age related; base; biological adaptation to stress; cell growth; fluorophore; functional decline; imaging probe; in vivo; intercellular communication; interest; luciferin; migration; molecular imaging; nerve stem cell; neurotransmission; oxidative damage; small molecule; tool

DESCRIPTION (provided by applicant): Reactive oxygen species (ROS) are a class of small molecules that play important roles in human health, aging, and disease. Imbalances in the production and consumption of ROS cause oxidative stress and damage of proteins, lipids, and nucleic acids, which can in turn lead to functional decline of tissues and organs over time and contribute to major diseases ranging from cancer to cardiovascular disorders to neurodegenerative diseases. At the same time, emerging data shows that one particular ROS, hydrogen peroxide (H2O2), can also be produced for physiological signaling purposes to mediate processes, from wound healing to neurotransmission, by regulating cell growth, differentiation, and migration pathways in a manner akin to the canonical small-molecule signal nitric oxide (NO). We are developing and applying new chemical tools for molecular imaging of H2O2 with the long-term goal of understanding how and in what context this oxygen metabolite contributes to normal physiology, aging, and disease. Specific aims for this competitive renewal submission include developing new probes that will allow chemoselective imaging of H2O2 with subcellular resolution, creating new imaging agents that can be used to monitor H2O2 fluxes in living organisms by near-IR fluorescence or bioluminescence modalities, and applying these and related chemical tools for elucidating the contributions of H2O2 production to signaling and stress pathways in neural stem cells and neurons.

说明(申请人提供)：活性氧(ROS)是一类在人类健康、衰老和疾病中发挥重要作用的小分子。ROS的产生和消耗的不平衡会导致氧化应激和蛋白质、脂类和核酸的破坏，随着时间的推移，这可能会导致组织和器官的功能衰退，并导致从癌症到心血管疾病到神经退行性疾病等重大疾病。与此同时，新的数据显示，一种特殊的ROS，过氧化氢(H_2O_2)，也可以被产生用于生理信号目的，通过调节细胞的生长、分化和迁移途径来调节从伤口愈合到神经传递的过程，其方式类似于典型的小分子信号一氧化氮(NO)。我们正在开发和应用新的化学工具来对过氧化氢进行分子成像，长期目标是了解这种氧代谢产物如何以及在什么背景下对正常生理、衰老和疾病做出贡献。这次竞争性更新提交的具体目标包括开发新的探针，以亚细胞分辨率进行过氧化氢的化学选择性成像，创造可用于通过近红外荧光或生物发光方式监测活体中过氧化氢通量的新成像剂，以及应用这些和相关的化学工具来阐明过氧化氢产生对神经干细胞和神经元中的信号和应激途径的贡献。