INTRACELLULAR RECEPTORS AND METABOLIC CONTROL

细胞内受体和代谢控制

• 批准号: 3755505
• 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/3755505
• 关键词: Xenopus oocyte; biological signal transduction; cadmium; carbohydrate transport; divalent cations; divalent metal; heavy metals; hexoses; insulin; ion transport; magnesium; mercury; metal poisoning; microinjections; phosphatase inhibitor; protein biosynthesis; receptor coupling; single cell analysis; 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), parafin 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, pervanadate, Cd++ and Zn++), which, at low concentrations, act as insulin mimics. We have found that vanadate and pervanadate stimulate hexose uptake by acting at intracellular sites and protein synthesis by acting at surface sites. Several observations indicate that vanadate, pervanadate and to a smaller extent insulin signal changes in protein synthesis by affecting Mg transport at the plasma membrane. First, rates of translation are particularly sensitive to microinjected, intracellular Mg. Second, stimulation of protein synthesis by vanadate, pervanadate and insulin depends on extracellular Mg, but not Ca; stimulation is reduced when Mg is reduced and exagerrated when Mg is raised. Third, exposing oocytes to vanadate, pervanadate or insulin causes a rapid, net influx of Mg. Future plans include: 1) characterizing further the detailed mechanisms by which insulin mimics affect the function of oocytes and somatic cells, 2) examining the role of intracellular Mg in metabolic control, and 3) determining if inappropriate cellular signalling is an important toxic effect of heavy metals that have insulin-like actions at low concentrations.

复杂的生物体使用化学信号，例如，激素和生长 要素，整合和协调专业功能 组织中 信息被转移到靶细胞时，化学 信号与特定的表面受体结合，结果，细胞 结构和功能会发生深刻的改变。 这个项目是 涉及在接收到这种信号之后发生的事件， 从表面传递信息的细胞内事件 细胞生化机制的受体。 研究信息如何 流向代谢控制点，我们已经开发出一种强大的 实验系统，由巨细胞（两栖动物卵母细胞）组成， 石蜡油基细胞显微注射和显微切割程序， 单细胞分析 最近的实验集中在 胰岛素和某些重金属盐（钒酸盐、过钒酸盐、Cd ++ 和Zn ++），其在低浓度下充当胰岛素模拟物。 我们有 发现钒酸盐和过钒酸盐通过作用于 细胞内位点和蛋白质合成通过作用于表面位点。 几个观察表明，钒酸盐，过钒酸盐和一个 胰岛素信号通过影响蛋白质合成而改变的程度较小 Mg在质膜上的转运。 首先，翻译速度是 对显微注射的细胞内Mg特别敏感。 第二、 钒酸盐、过钒酸盐和胰岛素刺激蛋白质合成 依赖于细胞外镁，但不依赖于钙;当镁 Mg含量增加时， 第三，暴露卵母细胞 钒酸盐、过钒酸盐或胰岛素引起Mg的快速净流入。 未来的计划包括：1）进一步描述详细机制 胰岛素模拟物通过其影响卵母细胞和体细胞的功能 细胞，2）检查细胞内镁在代谢控制中的作用， 和3）确定不适当的细胞信号传导是否是重要的 低浓度时具有胰岛素样作用的重金属的毒性作用 浓度的