INFLAMMATATION, IRON AND FERRITINS IN IRON ABSORPTION

有待检验的假设是，肝硬化患者血清铁蛋白的变化 起源是调节肠道铁吸收的信号。 的 当前的目标是：首先，了解某些细胞因子和 铁单独或协同调节血清铁蛋白分泌 并比较这种调节的机制， 初步的数据表明， 细胞溶质铁蛋白的翻译调节;第二，进一步 表征分泌和胞质之间的结构差异 铁蛋白;以及，最后，以确定是否铁吸收， 将各种形式的分泌铁蛋白静脉内给予大鼠 以确定肠道对铁的吸收是否改变。 的 研究设计包括继续使用物理技术，如 沉降速度和平衡离心， 电子显微镜分析血清的总体大小和形状 铁蛋白及其N-末端和内部氨基酸的测定 直接来自蛋白质亚基和来自克隆的 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 单独或联合铁、细胞因子IL-1和TNF测定 组合，NO作为调节剂的作用将通过以下方式定量： 用35 S-蛋氨酸代谢标记蛋白质， 免疫电泳 将输注分离形式的血清铁蛋白 在完整的缺铁大鼠和吸收放射性铁 （59 FeC 13）使用结扎的上肠段测量， 麻醉大鼠。 拟议研究的意义在于， 它将决定是否以及如何改变SFt水平的关系， 炎症和铁状态，并检查SFt是否在 控制铁的吸收。 这一点很重要，因为 目前在分子水平上了解这些过程， 畸变导致慢性过度吸收和铁超负荷。 这 是一种适应性反应，但人们对此知之甚少。

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.