Nuclear ferritin in corneal epithelial cells: tissue-specific nuclear transport and protection from UV-damage
Nuclear ferritin in corneal epithelial cells: tissue-specific nuclear transport and protection from UV-damage
复制标题
DOI：
10.1016/j.preteyeres.2004.08.004
复制
发表时间：
2005-03-01
影响因子：
17.8
通讯作者：
Fitch, JM
中科院分区：
文献类型：
--
作者：
Linsenmayer, TF;Cai, CX;Fitch, JM
我们已经确定了铁蛋白的重链作为一个发育调控的胚胎鸡角膜上皮细胞的核蛋白。核铁蛋白被组装成超分子形式，其与在其他细胞类型中发现的铁蛋白的细胞质形式难以区分。因此，它很可能具有铁螯合能力。游离铁。通过芬顿反应。已知会加剧紫外线诱导的和其他对细胞成分的氧化损伤，包括UNA。由于角膜上皮细胞不断暴露于紫外线下，我们假设核铁蛋白可能保护这些细胞的DNA免受自由基损伤。为了测试这种可能性，对来自角膜上皮和其他组织的细胞的原代培养物进行UV照射。并通过原位3 ′-末端标记分析检测对DNA的损伤。与该假设一致，具有核铁蛋白的角膜上皮细胞的DNA断裂比检查的其他细胞类型显著更少。然而，当核铁蛋白的表达被抑制时，细胞现在变得更容易受到UV诱导的DNA损伤。由于铁蛋白通常是细胞质，角膜上皮细胞必须有一个机制，影响其核定位。我们已经确定，这涉及到一个核转运分子，它与铁蛋白结合并将其带入细胞核。这种转运蛋白，我们称之为类铁蛋白，因为它与铁蛋白相似，至少有两个域。一个结构域是铁蛋白样的，负责结合铁蛋白。另一个域包含负责影响核运输的核定位信号。因此。似乎角膜上皮细胞已经进化出一种新的基于核铁蛋白的机制，用于保护它们的DNA免受UV损伤。另外。由于类铁蛋白在结构上类似于铁蛋白，因此它可以代表从其转运的分子进化而来的核转运蛋白的实例（即，铁蛋白）。(C)2004 Elsevier Ltd.保留所有权利。
We have identified the heavy chain of ferritin as a developmentally regulated nuclear protein of embryonic chicken corneal epithelial cells. The nuclear ferritin is assembled into a supramolecular form that is indistinguishable from the cytoplasmic form of ferritin found in other cell types. Thus it most likely has iron-sequestering capabilities. Free iron. via the Fenton reaction. is known to exacerbate UV-induced and other oxidative damage to cellular components, including UNA. Since corneal epithelial cells are constantly exposed to UV light, we hypothesized that the nuclear ferritin might protect the DNA of these cells from free radical damage. To test this possibility, primary cultures of cells from corneal epithelium and other tissues were UV irradiated. and damage to DNA was detected by an in situ 3'-end labeling assay. Consistent with the hypothesis, corneal epithelial cells with nuclear ferritin had significantly less DNA breakage than the other cells types examined. However, when the expression of nuclear ferritin was A inhibited the cells now became much more susceptible to UV-induced DNA damage. Since ferritin is normally cytoplasmic, corneal epithelial cells must have a mechanism that effects its nuclear localization. We have determined that this involves a nuclear transport A molecule which binds to ferritin and carries it into the nucleus. This transporter, which we have termed ferritoid for its similarity to ferritin, has at least two domains. One domain is ferritin-like and is responsible for binding the ferritin. the other domain contains a nuclear localization signal that is responsible for effecting the nuclear transport. Therefore. it seems that corneal epithelial cells have evolved a novel, nuclear ferritin-based mechanism for protecting their DNA against UV damage. In addition. since ferritoid is structurally similar to ferritin, it may represent an example of a nuclear transporter that evolved from the molecule it transports (i.e., ferritin). (C) 2004 Elsevier Ltd. All rights reserved.