INTRACELLULAR RECEPTORS AND METABOLIC CONTROL

细胞内受体和代谢控制

• 批准号: 3841163
• 负责人: D S MILLER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3841163
• 关键词: biological signal transduction; carbohydrate metabolism; cytotoxicity; egg /ovum; environmental toxicology; free radicals; genetic translation; hexoses; insulin; magnesium; microinjections; peroxides; protein biosynthesis; salts; single cell analysis; toxicant interaction; vanadium; zinc

Complex organisms use chemical signals, e.g., hormones and growth factors, to integrate and coordinate the function of specialized tissues. Information is transferred to target cells when chemical signals bind to specific surface receptors and, as a result, cell structure and function can be profoundly altered. This project is concerned with events that occur after such signals are received, intracellular events that transmit the information from the surface receptor to the cell's biochemical machinery. To study how information flows to metabolic control points, we have developed a powerful experimental system, consisting of a giant cell (amphibian oocyte), paraffin oil-based cell microinjection and microdissection procedures and single cell analyses. Recent experiments have focussed on the actions of insulin and certain heavy metal salts (vanadate and Zn++), which, at low concentrations, act as insulin mimics. We found that a peroxide of vanadate (pervanadate) rather than vanadate itself is the form of the ion that stimulates hexose uptake and protein synthesis. In addition hexose uptake, but not protein synthesis, is stimulated by microinjected, intracellular pervanadate. Pervanadate stimulates protein synthesis (but not hexose uptake) by a Mg-dependent mechanism, increasing Mg influx at the surface membrane. Since translation is particularly sensitive to intracellular Mg, increased influx appears to signal increased translation. Future plans include: 1) determining the mechanisms by which external and internal pervanadate affect the function of oocytes and somatic cells, 2) examining the role of intracellular Mg in metabolic control, and 3) determining how other heavy metal ions, which act as insulin mimics at low concentrations, disrupt cellular control mechanisms.

复杂的生物体使用化学信号，例如，激素和生长因子， 整合和协调专门组织的功能。 当化学信号与靶细胞结合时， 特定的表面受体，从而影响细胞结构和功能 可以被彻底改变。 这个项目关注的是 发生在这些信号被接收后，细胞内事件， 从表面受体到细胞生化反应的信息 机械. 为了研究信息如何流向代谢控制点，我们 开发了一个强大的实验系统，由一个巨大的细胞组成， （两栖类卵母细胞），石蜡油基细胞显微注射和 显微切割程序和单细胞分析。 最近的实验 已经集中在胰岛素和某些重金属盐的作用上 （钒酸盐和Zn++），其在低浓度下充当胰岛素模拟物。 我们发现钒酸盐的过氧化物（过钒酸盐）而不是钒酸盐， 它本身是刺激己糖摄取和蛋白质的离子形式 合成. 此外，己糖摄取，而不是蛋白质合成， 通过显微注射的细胞内过钒酸盐刺激。 过钒 刺激蛋白质合成（但不是己糖摄取）由镁依赖 机制，增加Mg流入的表面膜。 即翻译 对细胞内镁特别敏感，增加的内流似乎 增加翻译。 未来的计划包括：1）确定 外部和内部过钒酸盐影响功能的机制 2）研究细胞内Mg在卵母细胞和体细胞中的作用， 代谢控制，和3）确定其他重金属离子， 作为低浓度的胰岛素模拟物， 机制等