CORNEAL-EPITHELIAL NUCLEAR FERRITIN AND U.V. PROTECTION

角膜上皮核铁蛋白和紫外线

基本信息

  • 批准号:
    7490435
  • 负责人:
  • 金额:
    $ 49.18万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-02-01 至 2010-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION: Ultraviolet (UV) light constitutes a major environmental insult to all exposed tissues of the body, including those comprising the cornea and other underlying ocular structures. UV-light can damage a wide variety of macromolecular components including DNA resulting, for example, in cancer. This damage can be direct, or it can be indirect through the generation of reactive oxygen species (ROS). Corneal epithelial (CE) cells, however, seem to be refractory to such damage. Cancers of these cells are rare, even though this tissue is transparent and exposed to mutagenic UV light and other sources of ROS. Previous studies suggest that one mechanism that CE cells have evolved to prevent damage to their DNA involves ferritin in a nuclear localization. This molecule seems to greatly diminish the effects of UV-produced ROS to DNA-most likely by sequestering free iron, which acts as a catalyst in generating hydroxyl radicals, the most damaging ROS. Other studies suggest that the nuclear localization of ferritin is effected by a nuclear transporter, which is termed "ferritoid". Ferritoid is comprised of two regions, one, which contains a nuclear localization signal (NLS) and is responsible for the nuclear transport, and another, which is involved in the binding to ferritin, which ferritoid subsequently carries into the nucleus. The mechanism of this interaction between ferritoid and ferritin, and the subsequent nuclear transport will be examined further. The fate of ferritoid following transport and whether phosphorylation is involved in regulating the transport will also be investigated. The mechanisms responsible for regulating the production of ferritin and ferritoid will also be examined. The studies will include whether the synthesis of these molecules is co-ordinate with one another and whether the synthesis of ferritin involves a unique type of translational regulation, which results in a low iron ferritin. Such a low iron ferritin may be highly efficient at iron sequestration and therefore protection against active ROS. For the synthesis of ferritoid, studies will involve whether "stress response elements" in the gene respond to ROS. Lastly, it will be determined whether the protection against damage by ROS provided by nuclear ferritin in CE-cells, can be afforded to other cell types in which ROS potentially have deleterious effects
描述:紫外线(UV)光对身体所有暴露的组织构成主要的环境伤害,包括那些构成角膜和其他潜在的眼部结构的组织。紫外线可以破坏包括DNA在内的多种大分子成分,从而导致癌症。这种损伤可以是直接的,也可以是通过活性氧(ROS)的产生间接的。然而,角膜上皮(CE)细胞似乎难以抵抗这种损伤。这些细胞的癌症是罕见的,即使这些组织是透明的,暴露在致突变的紫外线和其他来源的活性氧。先前的研究表明,CE细胞进化出一种防止DNA损伤的机制与核定位中的铁蛋白有关。这种分子似乎大大减少了紫外线产生的活性氧对dna的影响——很可能是通过隔离游离铁来实现的,游离铁是产生羟基自由基的催化剂,羟基自由基是最具破坏性的活性氧。其他研究表明,铁蛋白的核定位受到核转运蛋白的影响,这种转运蛋白被称为“类铁蛋白”。铁素体由两个区域组成,一个区域包含核定位信号(NLS)并负责核运输,另一个区域参与与铁蛋白的结合,铁素体随后将铁蛋白带入细胞核。铁素体和铁蛋白相互作用的机制以及随后的核转运将进一步研究。转运后铁素体的命运以及磷酸化是否参与调节转运也将被研究。还将研究调节铁蛋白和类铁蛋白产生的机制。这些研究将包括这些分子的合成是否相互协调,以及铁蛋白的合成是否涉及一种独特的翻译调节类型,从而导致铁蛋白含量低。这种低铁铁蛋白可能在铁隔离方面效率很高,因此对活性氧具有保护作用。对于类铁蛋白的合成,研究将涉及基因中的“应激反应元件”是否对ROS有反应。最后,核铁蛋白在ce细胞中提供的对ROS损伤的保护是否可以提供给其他类型的细胞,其中ROS可能具有有害作用,这将是确定的

项目成果

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THOMAS Frank LINSENMAYER其他文献

THOMAS Frank LINSENMAYER的其他文献

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{{ truncateString('THOMAS Frank LINSENMAYER', 18)}}的其他基金

Developmental Regulation of Corneal Innervation
角膜神经支配的发育调节
  • 批准号:
    7579454
  • 财政年份:
    2009
  • 资助金额:
    $ 49.18万
  • 项目类别:
Developmental Regulation of Corneal Innervation
角膜神经支配的发育调节
  • 批准号:
    8002012
  • 财政年份:
    2009
  • 资助金额:
    $ 49.18万
  • 项目类别:
Developmental Regulation of Corneal Innervation
角膜神经支配的发育调节
  • 批准号:
    7752507
  • 财政年份:
    2009
  • 资助金额:
    $ 49.18万
  • 项目类别:
Functions of Bowman's Membrane and its Type V Collagen
鲍曼氏膜及其 V 型胶原蛋白的功能
  • 批准号:
    6415061
  • 财政年份:
    2001
  • 资助金额:
    $ 49.18万
  • 项目类别:
CORNEAL EPITHELIAL NUCLEAR FERRITIN AND UV PROTECTION
角膜上皮核铁蛋白和紫外线防护
  • 批准号:
    6166446
  • 财政年份:
    2001
  • 资助金额:
    $ 49.18万
  • 项目类别:
Corneal-Epithelial Nuclear Ferritin and U.V. Protection
角膜上皮核铁蛋白和紫外线
  • 批准号:
    8186017
  • 财政年份:
    2001
  • 资助金额:
    $ 49.18万
  • 项目类别:
Corneal-Epithelial Nuclear Ferritin and U.V. Protection
角膜上皮核铁蛋白和紫外线
  • 批准号:
    8719109
  • 财政年份:
    2001
  • 资助金额:
    $ 49.18万
  • 项目类别:
Functions of Bowman's Membrane and its Type V Collagen
鲍曼氏膜及其 V 型胶原蛋白的功能
  • 批准号:
    6641259
  • 财政年份:
    2001
  • 资助金额:
    $ 49.18万
  • 项目类别:
Functions of Bowman's Membrane and its Type V Collagen
鲍曼氏膜及其 V 型胶原蛋白的功能
  • 批准号:
    6524801
  • 财政年份:
    2001
  • 资助金额:
    $ 49.18万
  • 项目类别:
Corneal-Epithelial Nuclear Ferritin and U.V. Protection
角膜上皮核铁蛋白和紫外线
  • 批准号:
    8322603
  • 财政年份:
    2001
  • 资助金额:
    $ 49.18万
  • 项目类别:

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