MOLECULAR DYNAMICS OF IRON REGULATION AND FUNCTION

铁调节和功能的分子动力学

• 批准号: 6626963
• 负责人: MICHAEL J CHORNEY
• 金额: $ 56.13万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626963
• 关键词: iron disorder; iron metabolism; transferrin receptor

The long-term goal of this Program Project and the Hershey Iron Group is to define the molecular and cellular interactions controlling iron regulation and function. The understanding of 1) the mechanisms of intestinal iron egress; 2) intracellular iron compartmentalization; 3) iron-mediated gene regulation; 4) intracellular iron-regulatory protein flux nd 5) the intricate cellular and molecular feedback mechanisms which maintain iron balance are all areas toward which the Program Project team is expected to contribute. Specifically, the individual aims are 1) to determine the structure, processing and expression of the hemochromatosis disease gene within the in vitro and in vivo systems and particularly in the context of iron challenge; 2) to study the regulation of the iron- regulatory proteins (IRPs) by focusing on post-transcriptional modifications and mechanisms of intracellular translocation following cytokine and iron stimulation; and 3) to understand the cytokine-induced molecular mechanisms effecting iron mobilization and flux within a well- defined, iron-loaded primary hepatocyte culture system. This Program Project draws together three research laboratories within the Pennsylvania State University College of Medicine with i) proven track records in the molecular biological and genetic studies of iron metabolism, ii) complementing research interests; iii) established collaborations and well-recognized synergy. The specific proposals, entitled "Biological function of the hemochromatosis disease gene" (Project 1-Chorney); "Post-transcriptional regulation of iron regulatory proteins" (Project 2-Conner) and "Molecular and cellular control transcriptional regulation of iron regulatory proteins" (Project 2-Conner) and "Molecular and cellular control mechanisms in iron-loaded hepatocytes" (Project 3-Isom) engender a natural connectedness which will facilitate the intellectual movement between systems. The Program Project will receive foundation support from a Core encompassing "Metal Analysis and Molecular Genetics" contained within the broader Division of Research Resources (Billingsley) which will further ensure cogent interactions through the sharing of reagents and technologies. It is anticipated that the group will contribute much to the understanding of the physiological processes underlying iron flux and utilization in both health and disease states such as iron overload and anemia, Alzheimer's disease and malignancy.

该计划项目和好时钢铁集团的长期目标是 定义控制铁的分子和细胞相互作用 调节和功能。 1) 机制的理解 肠道铁排出量； 2）细胞内铁的区室化； 3） 铁介导的基因调控； 4) 细胞内铁调节蛋白 Flux nd 5）复杂的细胞和分子反馈机制 维持铁平衡是项目团队致力于的所有领域 预计将做出贡献。具体来说，个人目标是 1) 确定血色素沉着症的结构、加工和表达 体外和体内系统中的疾病基因，特别是 铁挑战的背景； 2）研究铁的调节 调节蛋白（IRP）通过关注转录后 细胞内易位的修饰和机制 细胞因子和铁刺激； 3）了解细胞因子诱导的 影响铁在井内流动和通量的分子机制 明确的载铁原代肝细胞培养系统。 该计划项目汇集了三个研究实验室 宾夕法尼亚州立大学医学院具有 i) 成熟的轨道 铁的分子生物学和遗传学研究记录 新陈代谢，ii) 补充研究兴趣； iii) 成立 合作和公认的协同作用。具体建议， 题为“血色素沉着病基因的生物学功能” （项目 1-Chorney）； “铁调控的转录后调控 蛋白质”（项目 2-Conner）和“分子和细胞控制 铁调节蛋白的转录调控”（项目 2-Conner） 和“载铁肝细胞的分子和细胞控制机制” （项目 3-Isom）产生一种自然的联系，这将促进 系统之间的智力运动。该计划项目将 获得核心的基础支持，包括“金属分析和 分子遗传学”包含在更广泛的研究部门内 资源（比林斯利）将进一步确保令人信服的互动 通过共享试剂和技术。预计 该小组将为理解生理学做出很大贡献 健康和疾病中铁通量和利用的基础过程 铁超载和贫血、阿尔茨海默氏病和 恶性肿瘤。

项目成果

Hemochromatosis protein (HFE) and tumor necrosis factor receptor 2 (TNFR2) influence tissue iron levels: elements of a common gut pathway?

血色素沉着蛋白 (HFE) 和肿瘤坏死因子受体 2 (TNFR2) 影响组织铁水平：共同肠道途径的要素？

• DOI: 10.1006/bcmd.2002.0565
• 发表时间: 2002
• 期刊: Blood cells, molecules & diseases
• 作者: Meyer,PaulN;Gerhard,GlennS;Yoshida,Yukinori;Yoshida,Mika;Chorney,KarenA;Beard,John;Kauffman,ElizabethJ;Weiss,Günter;Chorney,MichaelJ
• 通讯作者: Chorney,MichaelJ

Vibrio vulnificus septicemia in a patient with the hemochromatosis HFE C282Y mutation.

血色素沉着病 HFE C282Y 突变患者的创伤弧菌败血症。

• DOI: 10.5858/2001-125-1107-vvsiap
• 发表时间: 2001
• 期刊: Archives of pathology & laboratory medicine
• 影响因子: 4.6
• 作者: Gerhard,GS;Levin,KA;PriceGoldstein,J;Wojnar,MM;Chorney,MJ;Belchis,DA
• 通讯作者: Belchis,DA

Gap junction-mediated intercellular communication in a long-term primary mouse hepatocyte culture system.

长期原代小鼠肝细胞培养系统中间隙连接介导的细胞间通讯。

• DOI: 10.1053/jhep.2003.50418
• 发表时间: 2003
• 期刊: Hepatology (Baltimore, Md.)
• 作者: Stoehr,StephanieA;Isom,HarrietC
• 通讯作者: Isom,HarrietC