CORNEAL EPITHELIAL NUCLEAR FERRITIN AND UV PROTECTION

描述：紫外线(UV)是对环境的一种主要侮辱 裸露的身体所有组织，包括构成角膜和 其他潜在的眼部结构。紫外光会损害多种 大分子成分，从DNA，到蛋白质，再到脂质，都有损害 例如，导致癌症的DNA。这种损害可以是直接的，也可以是 通过产生活性氧物种(AOS)间接产生。角膜 然而，上皮(CE)细胞似乎对这种损伤难以抵抗。癌症 其中的细胞是异常罕见的，尽管这个组织是 透明，并持续暴露在诱变紫外线和其他来源的 过氧化氢等AOS。我们的结果表明，CE细胞具有的一种机制 进化以防止对其DNA的损害涉及到细胞核中的铁蛋白 定位，而不是它在所有其他细胞中的细胞质位置 类型。这种分子似乎直接减弱了紫外线产生的AOS的影响。 对DNA和可能的其他核组件-最有可能是无隔离 作为产生羟基自由基的催化剂的铁，最 破坏AOS。有待进一步研究的领域：1)机制 参与CE细胞中铁蛋白的核定位，2)这是如何 分子保护DNA免受紫外线和其他氧化损伤，以及3)如何 这种分子的生产受到发育的调节。对于核能来说 在CE细胞中的定位将被研究两种可能的机制。一个是 涉及CE组织特异性伴侣蛋白，能够携带 铁蛋白“背着”进入细胞核，另一个是一些 特化的CE细胞核本身负责运输。 那么铁封存在减少紫外线对DNA损伤中的作用 将进一步评估CE细胞的数量。还将确定这一点是否 保护扩展到其他AOS来源，以及类似的保护是否可以 提供给紫外线诱导的其他类型的细胞和其他来源的AOS 有潜在的有害影响。最后，对生产的调节。 将对核铁蛋白进行研究--主要在铁蛋白前期的早期阶段 我们的初步数据表明，它可能属于一种独特的类型 翻译调节涉及低水平的铁和另一个 成分(S)，如甲状腺素。这种机制可能会产生低铁的铁蛋白 这在铁的隔离方面是非常有效的，因此可以防止 AOS造成的损害。

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 ranging from DNA, to proteins, to lipids, with damage to DNA resulting, for example, in cancer. This damage can be direct, or it can be indirect through the generation of active oxygen species (AOS). Corneal epithelial (CE) cells, however, seems to be refractory to such damage. Cancers of these cells are extra-ordinarily rare, even though this tissue is transparent and constantly exposed to mutagenic UV light and other sources of AOS such as H2O2. Our results suggest that one mechanism that CE cells have evolved to prevent damage to their DNA involves ferritin in a nuclear localization, rather than the cytoplasmic location it has in all other cell types. This molecule seems to directly diminish the effects of UV-produced AOS to DNA and possibly other nuclear components-most likely be sequestering free iron which acts as a catalyst in generating hydroxyl radicals, the most damaging AOS. The areas that will be investigated further: 1) the mechanisms involved in the nuclear localization of ferritin in CE cells, 2) how this molecule protects DNA from UV-induced and other oxidative damage, and 3) how production of the molecule is developmentally regulated. For the nuclear localization in CE cells two possible mechanisms will be examined. One is the involvement of a CE tissue-specific chaperone that is capable of carrying ferritin "piggy-back" into the nucleus, and the other is that some specialization of the CE cell nucleus itself is responsible for the transport. Then the role of iron sequestration in decreasing UV-induced damage to the DNA of CE cells will be evaluated further. It will also be determined whether this protection extends to other sources of AOS, and whether similar protection can be afforded to other cell types in which UV-induced and other sources of AOS potentially have deleterious effects. Lastly, the regulation of production of nuclear ferritin will be investigated-chiefly at the early, pre-ferritin stage of development, which our preliminary data suggest may be under a unique type of translational regulation involving low levels of iron plus another component(s) such as thyroxine. This mechanism may produce a low-iron ferritin that is highly efficient at iron sequestration and therefore protection against damage by AOS.