INFLAMMATATION, IRON AND FERRITINS IN IRON ABSORPTION

铁吸收中的炎症、铁和铁蛋白

• 批准号: 6029665
• 负责人: MARIA C LINDER
• 金额: $ 0.75万
• 依托单位: CALIFORNIA STATE UNIVERSITY FULLERTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6029665
• 关键词: biological signal transduction; centrifugation; cytokine; electron microscopy; ferritin; gastrointestinal absorption /transport; genetic transcription; immunoelectrophoresis; inflammation; interleukin 1; iron; iron metabolism; laboratory rat; liver cells; liver metabolism; molecular cloning; nitric oxide; protein biosynthesis; protein structure function; sedimentation velocity; tumor necrosis factor alpha

The hypothesis to be tested is that changes in serum ferritin of hepatic origin are the signal for regulating intestinal iron absorption. The immediate goals are: first, to understand how certain cytokines and iron, individually and in concert, regulate secretion of serum ferritin by hepatic cells and to compare the mechanism of this regulation which preliminary data suggest is transcriptional in contrast to the translational regulation of cytosolic ferritin; second, to further characterize the structural differences between secreted and cytosolic ferritins; and, finally, to determine whether iron absorption by administering various forms of secreted ferritin intravenously into rats to establish whether iron absorption by the intestine is altered. The research design includes continues use of physical techniques such as sedimentation velocity and equilibrium centrifugation together with electron microscopy to analyze the overall size and shape of the serum ferritin and determination of N-terminal and internal amino acid sequences both directly from the protein subunits and from the cloned cDNA, carbohydrate content using lectin binding and glycosidase treatment. The rate and extent of ferritin biosynthesis will be determined in response to iron, cytokines IL-1 and TNF, alone or in combination, and the role of NO as a regulator will be quantitated by metabolically labeling the protein with 35S-Methionine and by immunoelectrophoresis. Isolated forms of serum ferritin will be infused in intact iron-deficient rats and the absorption in radioactive iron (59FeC13) measured using tied off upper intestinal segments in anesthetized rats. The significance of the proposed research is that it will determine whether and how levels of SFt change in relations to inflammation and iron status and examine whether SFt plays a role in controlling iron absorption. This is important since very little is currently known about these process at the molecular level and aberrations result in chronic over-absorption and iron overload. This is an adaptive response which is poorly understood.

要检验的假设是肝的血清铁蛋白的变化 起源是调节肠道吸收的信号。 这 直接目标是：首先，了解某些细胞因子和如何 铁，单独和共同调节血清铁蛋白的分泌 通过肝细胞并比较该调节的机制 初步数据表明，与 胞质铁蛋白的翻译调节；其次，进一步 表征分泌和胞质之间的结构差异 铁蛋白；最后，确定是否通过 将各种形式的分泌铁蛋白静脉注射到大鼠中 确定肠吸收是否改变。 这 研究设计包括继续使用物理技术，例如 沉积速度和平衡离心 电子显微镜分析血清的整体尺寸和形状 铁蛋白和N端和内氨基酸的测定 直接来自蛋白质亚基和克隆的序列 cDNA，使用凝集素结合和糖苷酶的碳水化合物含量 治疗。 铁蛋白生物合成的速率和程度将是 根据铁，Cytokines IL-1和TNF的响应，单独或在 组合以及NO作为监管机构的作用将由 代谢将蛋白质标记为35s-甲硫代和 免疫电泳。 血清铁蛋白的孤立形式将被注入 在完整的铁缺陷大鼠中，放射性铁的吸收 （59fec13）使用绑定的上肠段测量 麻醉大鼠。 拟议的研究的意义是 它将确定SFT的关系是否以及如何变化 炎症和铁状态，并检查SFT是否在 控制铁吸收。 这很重要，因为很少 目前在分子水平上了解这些过程以及 畸变导致长期吸收和铁超载。 这 是一种自适应反应，知之甚少。