FLOURESCENT TOOLS FOR THE STUDY OF METALLOTHIONEIN

用于研究金属硫蛋白的荧光工具

• 批准号: 7111537
• 负责人: CHRISTOPHER J. FREDERICKSON
• 金额: $ 33.85万
• 依托单位: NEUROBIOTEX, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-21 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7111537
• 关键词: metallothionein; proteins; zinc

DESCRIPTION (provided by applicant): We will deliver to life scientists fluorescent tools for the study of metallothionein and metallothionein- zinc signaling. Metallothionein-zinc signals have recently emerged as central step in many life-or-death signal pathways, including proliferation, apoptosis and metastasis. Arguably, MT-zinc signaling rivals calcium-calmodulin, IP3, and nitric oxide in ubiquity and essentiality. In action, the metallated protein, metallothionein (MT) can release 7 zinc ions into solution under oxidative or nitrosative stimulation (Fig 1). Conversely, The non-metalated protein, thionein (T) can sequester 7 zinc ions, terminating a zinc signal. Even more intriguing, both T and MT show evidence of moving through both plasma and organelle membranes, thus allowing zinc signals to be transposed among and between those compartments. We will deliver T and MT proteins that are labeled with fluorescent reporters at specific positions. These reporters constitute fluorescence-resonance-energy-transfer (FRET) systems that change color (emission spectra) when zinc is bound or released (Fig. 2). Because these proteins can be coaxed into tissues and thence into cytosol from the circulation, they can be used for both in vitro and in vivo research. With appropriate endoscopic and transdermal confocal or two-photon microscopy MT/T signaling can potentially be imaged in vivo and in vitro. MT/T and zinc signaling are integral to cell injury and death pathways as well as both metastatic and .healthy cell growth. Our tools will facilitate research in all of those areas and contribute to the advancement and development of diagnostic and therapeutic medical science.

描述（由申请人提供）：我们将向生命科学家提供荧光工具，以研究金属硫硫代蛋白和金属硫蛋白锌信号传导。金属硫蛋白锌信号最近已成为许多生命或死亡信号途径的中心步骤，包括增殖，凋亡和转移。可以说，MT-Zinc信号传导在普遍性和重要性中竞争钙 - 钙统和一氧化氮。在作用中，金属蛋白质，金属硫硫代蛋白（MT）可以在氧化或硝化刺激下释放7个锌离子（图1）。相反，非金属蛋白硫依蛋白（T）可以隔离7个锌离子，从而终止锌信号。更有趣的是，T和MT都显示出通过血浆和细胞器膜移动的证据，从而使锌信号可以在这些隔室之间进行转移。我们将提供T和MT蛋白，这些蛋白在特定位置标记为荧光记者。这些记者构成荧光 - 谐振 - 能量转移（FRET）系统，这些系统会在固定或释放锌时改变颜色（发射光谱）（图2）。由于这些蛋白质可以从循环系统中哄骗到组织中，从而进入细胞质，因此可以用于体外和体内研究。使用适当的内窥镜和透皮共聚焦或两光子显微镜MT/T信号传导可能会在体内和体外成像。 MT/T和锌信号传导是细胞损伤和死亡途径以及转移性和健康细胞生长不可或缺的一部分。我们的工具将促进所有这些领域的研究，并有助于诊断和治疗医学的发展和发展。