REGULATORY EFFECTS OF HEME TRANSPORT INTO LIVER CELLS

血红素转运至肝细胞的调节作用

基本信息

批准号：
3244458
负责人：
JAWED ALAM
金额：
$ 9.17万
依托单位：
OCHSNER CLINIC FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-09-15 至 1995-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3244458
关键词：
DNA binding protein enzyme induction /repression gene expression heme hemopexin intracellular transport liver cells liver metabolism metallothionein molecular cloning nucleic acid sequence oxygenases protein purification receptor expression receptor mediated endocytosis site directed mutagenesis transcription factor

项目摘要

The transport of heme by the plasma protein, hemopexin, into tissues such as the liver is a specific, receptor-mediated process. As a result of this hepatic reclamation of heme, biologically useful iron is conserved, the accumulation of toxic heme is prevented and the growth of invading microorganisms is inhibited. The ultimate goals of our research are 1) to delineate the biochemical mechanism of heme transport by hemopexin - from the initial binding of heme in the circulation to the final intracellular localization of heme and heme-iron - and 2) to identify and characterize the intracellular consequences of hemopexin-mediated heme transport. With regards to this second objective, recent studies in this laboratory indicate that hemopexin-mediated heme transport modulates gene expression, including the induction of heme oxygenase and metallothionein synthesis and down-regulation of the synthesis of the transferrin receptor. The major goal of this proposal then is to characterize the mechanisms by which hemopexin-mediated heme transport into liver cells stimulates the expression of heme oxygenase and metallothionein. In particular, we will: 1) identify and determine the mode of action of specific DNA sequences that are involved in the heme-hemopexin-dependent stimulation of heme oxygenase and metallothionein gene transcription; 2) characterize these DNA sequence elements with respect their specific protein binding capacity; 3) isolate and characterize the DNA-binding proteins involved this regulation.

血红素通过血浆蛋白血红素结合蛋白转运到组织中，例如因为肝脏是一个特定的、受体介导的过程。结果是肝回收血红素，保留生物学上有用的铁，防止有毒血红素的积累和入侵细胞的生长微生物受到抑制。我们研究的最终目标是 1）描述血红素通过血红素转运的生化机制 - 来自循环中血红素与最终细胞内的最初结合血红素和血红素铁的定位 - 以及 2) 识别和表征血红素结合蛋白介导的血红素运输的细胞内后果。和关于第二个目标，该实验室最近的研究表明血红素介导的血红素转运调节基因表达，包括诱导血红素加氧酶和金属硫蛋白的合成下调转铁蛋白受体的合成。主要该提案的目标是描述机制的特征血红素介导的血红素转运至肝细胞刺激血红素加氧酶和金属硫蛋白的表达。特别是，我们将： 1）识别并确定特定DNA的作用方式参与血红素-血红素依赖性的序列刺激血红素加氧酶和金属硫蛋白基因转录； 2) 描述这些 DNA 序列元素的特征它们的特定蛋白质结合能力； 3) 分离并表征所涉及的 DNA 结合蛋白本规定。