INFLAMMATATION, IRON AND FERRITINS IN IRON ABSORPTION

需要检验的假设是肝脏血清铁蛋白的变化 来源是调节肠道铁吸收的信号。这个 眼前的目标是：首先，了解某些细胞因子和 铁单独或协同调节血清铁蛋白的分泌 通过肝细胞，比较这一调节机制 初步数据表明，这是转录的，而不是 胞质铁蛋白的翻译调控；第二，进一步 描述分泌型和胞浆型的结构差异 铁质；最后，确定铁的吸收是否由 大鼠静脉注射不同形式的分泌型铁蛋白 以确定肠道对铁的吸收是否发生了变化。这个 研究设计包括继续使用物理技术，如 沉降速度和平衡离心法 用电子显微镜分析血清的整体大小和形状 铁蛋白与N-末端和内源氨基酸的测定 直接从蛋白质亚基和从克隆的 用凝集素结合和糖苷酶测定cDNA、碳水化合物含量 治疗。铁蛋白生物合成的速度和程度将是 对铁、细胞因子IL-1和肿瘤坏死因子的反应，单独或 结合在一起，NO作为调节器的作用将被量化为 用~(35)S-蛋氨酸代谢性标记蛋白质 免疫电泳法。单独形式的血清铁蛋白将被注入 正常缺铁大鼠体内放射性铁的吸收 (59FeC13)用结扎的上肠段测量 麻醉大鼠。拟议研究的意义在于 它将确定SFT水平是否以及如何变化与以下方面的关系 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，因为很少有 目前在分子水平上已知这些过程和 异常会导致慢性过度吸收和铁超载。这 是一种适应性反应，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.