Ferritin is a developmentally regulated nuclear protein of avian corneal epithelial cells

Ferritin is a developmentally regulated nuclear protein of avian corneal epithelial cells
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DOI:
10.1074/jbc.272.19.12831
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发表时间:
1997-05-09
影响因子:
4.8
通讯作者:
Linsenmayer, TF
Linsenmayer, TF
中科院分区:
生物学2区
文献类型:
--
作者:
Cai, CX;Birk, DE;Linsenmayer, TF

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我们现在已经观察到,其中一组抗体与发育调节的角膜上皮细胞核成分发生反应。这一组分是铁蛋白的重链,通过对免疫分离的cDNA克隆和蛋白质的免疫印迹分析确定。免疫印迹还表明,核铁蛋白可能是一种超分子形式,类似于许多细胞的细胞质中发现的铁结合铁蛋白复合体。体外培养和转染研究表明,细胞核的定位主要取决于细胞类型,但可以被体外环境改变。核铁蛋白的出现至少部分是在翻译调控下的,众所周知,对于细胞质形式的分子是真实的,分子的组织和发育的mRNA的分布比蛋白质本身广泛得多,并且用铁螯合剂去铁胺从角膜上皮细胞培养中去除铁阻止了核铁蛋白的出现。目前,核铁蛋白的功能作用(S)仍不清楚,但以前对细胞质铁蛋白的研究提出了这种可能性,即它通过隔离铁来防止自由基生成(“氧化应激”)造成的损害,虽然核铁蛋白是否可以防止氧化损伤还有待测试,但我们发现这是一种很有吸引力的可能性,因为角膜上皮是透明的,并且经常暴露在产生自由基的紫外光下,所以有可能这个组织的细胞已经进化出一种专门的机制来防止其核成分的氧化损伤。
We have now observed that one group of these antibodies reacts with a developmentally regulated component of corneal epithelial cell nuclei. This component is the heavy chain of ferritin, as determined by analyses of immunoisolated cDNA clones and immunoblotting of the protein. Immunoblotting also suggests that the nuclear ferritin may be in a supramolecular form that is similar to the iron-binding ferritin complex found in the cytoplasm of many cells. In vitro cultures and transfection studies show that the nuclear localization depends predominantly on cell type but can be altered by the in vitro environment. The appearance of nuclear ferritin is at least partially under translational regulation, as is known to be true for the cytoplasmic form of the molecule, The tissue and developmental distributions of the mRNA for the molecule are much more extensive than the protein itself, and the removal of iron from cultures of corneal epithelial cells with the iron chelator deferoxamine prevents the appearance of nuclear ferritin. At present the functional role(s) of nuclear ferritin remain unknown, but previous studies on cytoplasmic ferritin raise the possibility that it prevents damage due to free radical generation (''oxidative stress'') by sequestering iron, Although it remains to be tested whether nuclear ferritin prevents oxidative damage, we find this an attractive possibility, Since the corneal epithelium is transparent and is constantly exposed to free radical-generating UV light, it is possible that the cells of this tissue have evolved a specialized mechanism to prevent oxidative damage to their nuclear components.