CORNEAL-EPITHELIAL NUCLEAR FERRITIN AND U.V. PROTECTION

产品说明：紫外线（UV）光构成对身体的所有暴露组织的主要环境损害，包括包含角膜和其它下方眼部结构的那些。紫外线可以破坏包括DNA在内的多种大分子成分，导致例如癌症。这种损害可以是直接的，也可以是通过产生活性氧（ROS）间接的。然而，角膜上皮（CE）细胞似乎对这种损伤不敏感。这些细胞的癌症是罕见的，即使这种组织是透明的，并暴露于诱变紫外线和其他来源的活性氧。以前的研究表明，CE细胞进化来防止其DNA损伤的一种机制涉及核定位中的铁蛋白。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，最有可能是通过螯合游离铁，游离铁在产生羟基自由基（最具破坏性的活性氧）中起催化剂的作用。其他研究表明，铁蛋白的核定位是由核转运蛋白，这是所谓的“类铁蛋白”的影响。类铁蛋白由两个区域组成，一个区域含有核定位信号（NLS）并负责核转运，另一个区域参与与铁蛋白的结合，类铁蛋白随后携带到细胞核中。类铁蛋白和铁蛋白之间的这种相互作用的机制，以及随后的核运输将进一步研究。运输后铁蛋白的命运以及磷酸化是否参与调节运输也将被研究。还将研究负责调节铁蛋白和类铁蛋白的产生的机制。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，从而导致低铁铁蛋白。这样的低铁铁蛋白在铁螯合方面可以是高度有效的，并且因此保护免受活性ROS的影响。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产生反应。最后，将确定CE-细胞中核铁蛋白提供的抗ROS损伤的保护是否可以提供给ROS可能具有有害作用的其他细胞类型

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