CORNEAL EPITHELIAL NUCLEAR FERRITIN AND UV PROTECTION

描述：紫外线（UV）光是一种主要的环境污染， 身体的所有暴露组织，包括构成角膜的组织， 其他潜在的眼部结构。紫外线可以破坏各种各样的 大分子成分，从DNA到蛋白质，再到脂质， 导致癌症的DNA。这种伤害可以是直接的，也可以是 通过产生活性氧（AOS）间接。角膜 然而，上皮（CE）细胞似乎对这种损伤不敏感。癌症 这些细胞是非常罕见的，即使这个组织是 透明，并不断暴露于诱变紫外线和其他来源的 AOS如H2 O2。我们的研究结果表明，CE细胞的一种机制是， 进化来防止DNA损伤的方法涉及到核内的铁蛋白， 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 DNA和其他可能的核成分-最有可能是螯合免费 铁在产生羟基自由基中充当催化剂， 破坏AOS将进一步研究的领域：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免受紫外线诱导和其他氧化损伤，以及3）如何 该分子的产生受到发育调节。为核 在CE细胞中的定位将检查两种可能的机制。一是 涉及CE组织特异性伴侣，其能够携带 铁蛋白“背驮”进入细胞核，另一个是，一些 CE细胞核本身的特化负责运输。 然后研究了铁螯合剂在降低紫外线对DNA损伤中的作用 将进一步评估CE细胞。还将确定这是否 保护延伸到AOS的其他来源，以及类似的保护是否可以 提供给其他细胞类型，其中UV诱导的和其他来源的AOS 可能会产生有害影响。最后，生产管理 核铁蛋白将主要在早期，前铁蛋白阶段进行研究 我们的初步数据表明，这可能是一种独特的类型， 低水平的铁和另一种 成分如甲状腺素。这种机制可能会产生一种低铁铁蛋白 这是非常有效的铁螯合，因此保护免受 AOS的伤害。

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.