REGULATORY EFFECTS OF HEME TRANSPORT INTO LIVER CELLS

血红素转运至肝细胞的调节作用

• 批准号: 3244456
• 负责人: JAWED ALAM
• 金额: $ 10.08万
• 依托单位: OCHSNER CLINIC FOUNDATION
• 依托单位国家: 美国
• 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/3244456
• 关键词: DNA binding protein; enzyme induction /repression; gene expression; heme; hemopexin; intracellular transport; liver cells; liver metabolism; metallothionein; molecular cloning; oxygenases; protein purification; receptor expression; receptor mediated endocytosis; site directed mutagenesis; transcription factor; DNA binding protein; enzyme induction /repression; gene expression; heme; hemopexin; intracellular transport; liver cells; liver metabolism; metallothionein; molecular cloning; oxygenases; protein purification; receptor expression; receptor mediated endocytosis; site directed mutagenesis; transcription factor

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转运到组织中 由于肝脏是一种特定的受体介导的过程。 结果 血红素，生物学上有用的铁的肝填海是保守的， 预防有毒血红素的积累，并侵入 微生物被抑制。 我们研究的最终目标是1） 描绘出血红素转运的生化机理 - 从 血红素在循环中与最终细胞内的初始结合 血红素和血红素铁的定位 - 和2）识别和表征 血红素介导的血红素转运的细胞内后果。 和 关于该实验室最近的第二个目标，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合成以及 转铁蛋白受体的合成下调。 专业 然后，该提案的目标是表征其机制 血红素介导的血红素转运到肝细胞刺激 血红素氧酶和金属硫硫蛋白的表达。 特别是，我们将： 1）识别并确定特定DNA的作用方式 涉及血红素血红素蛋白依赖的序列 刺激血红素加氧酶和金属硫蛋白基因 转录； 2）尊重这些DNA序列元件 它们的特定蛋白质结合能力； 3）分离并表征涉及的DNA结合蛋白 这个法规。