Ferritin, Iron Homeostasis and Cellular Stress

铁蛋白、铁稳态和细胞压力

• 批准号: 7891073
• 负责人: FRANK M. TORTI
• 金额: $ 10万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-17 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7891073
• 关键词: Animals; Antioxidants; Binding Proteins; Cells; Cellular Stress; Chemopreventive Agent; Complex; Disease; Elements; FOS gene; Ferritin; H ferritin; Health; Histone Deacetylation; Homeostasis; Iron; Iron-Binding Proteins; Knockout Mice; Maps; Mediating; Methods; Molecular; Molecular Biology; Molecular Weight; Oxidants; Oxidative Stress; Pathway interactions; Phenotype; Predisposition; Reactive Oxygen Species; Regulation; Repression; Response Elements; Role; Stimulus; Stress; Structure; TP53 gene; Testing; Tetracyclines; Tissues; Transgenic Mice; Transgenic Organisms; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Xenobiotics; cytokine; in vivo; mouse model; mutant; promoter; response; response to injury; vector

DESCRIPTION (provided by applicant): The metallochemistry and molecular biology of iron converge in the study of ferritin structure and function. Ferritin is an iron binding protein whose regulation, once thought to be responsive only to changes in cellular iron content, has more recently been shown to be targeted by stress-induced stimuli, including cytokines, oxidants, and a range of xenobiotics. We now know that agents such as tumor necrosis factor, reactive oxygen species, and other stimuli trigger ferritin induction; ferritin, in turn, alters cellular iron homeostasis by sequestering reactive, "low molecular weight" cellular iron. This in turn reduces susceptibility to subsequent stress. In this proposal we explore the hypothesis that ferritin regulation is instrumental in modulating the magnitude and character of the cellular response to injury and stress. We examine the unique contribution of ferritin to the phenotype of cells and tissues exposed to prooxidants and antioxidants. In our first Specific Aim, we explore the molecular mechanisms by which ferritin participates in the chemopreventive response to prooxidant xenobiotics. In our second Specific Aim, we explore potential pathways by which oxidative stress regulates ferritin in health and disease. In our third Specific Aim, we develop in vivo mouse models to test the relevance of our findings in the context of whole animals.

描述（申请人提供）：金属化学和分子生物学