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.

描述（由申请人提供）：活性氧（ROS）是一类小分子，在人类健康，衰老和疾病中起重要作用。 ROS的生产和消耗的失衡会导致氧化应激和蛋白质，脂质和核酸的损害，这反过来又会导致随着时间的推移组织和器官的功能下降，并导致从癌症到心血管疾病到神经减退症的主要疾病。同时，新兴数据表明，也可以通过调节细胞生长，分化和迁移途径，以某种方式调节一种特定的ROS（H2O2氢（H2O2）（H2O2），用于生理信号传导目的，以介导从伤口愈合到神经传递的过程类似于规范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用于H2O2的分子成像，其长期目标是了解这种氧代谢物如何以及在什么情况下有助于正常的生理，衰老和疾病。该竞争性更新提交的具体目的包括开发新的探针，这些探针将允许使用亚细胞分辨率对H2O2进行化学选择性成像，从而创建可用于通过近IIR荧光或生物发光的生物体中的H2O2通量来监视H2O2磁通量的新成像剂相关的化学工具，用于阐明H2O2产生对神经干细胞和神经元信号传导和应激途径的贡献。