Abstract
Previously, we generated monoclonal antibodies against chicken corneal cells (Zak, N. B., and Linsenmayer, T. F. (1983) Dev. Biol. 99, 373). 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.
Highlights
Nuclei contain a myriad of different proteins as well as nucleic acids
It remains to be tested whether the nuclear ferritin prevents oxidative damage, we find this an attractive possibility since the corneal epithelium is transparent and is constantly exposed to active oxygen species (AOS)-generating UV light
The results of the present study show that during development of the avian corneal epithelium, ferritin is a developmentally regulated nuclear protein
Summary
Nuclei contain a myriad of different proteins as well as nucleic acids. Nuclear proteins range from general ones, such as the histones that are universally present in cells and determine the structure of chromatin, to the DNA-binding regulatory proteins, some of which are cell-specific and developmentally regulated. In the present study we have observed that when immunofluorescence analyses are performed on corneal tissue sections or cell cultures fixed with paraformaldehyde, the antigen is localized predominantly, if not exclusively, within the nuclei of the epithelial cells. We have characterized the nuclear antigen as the heavy chain of ferritin (ferritin-H) and have shown that it is assembled into the same supramolecular complex that is found in the cytoplasm of many other types of cells [1] It is potentially capable of sequestering iron. At present the functional role(s) of the nuclear ferritin remain unknown, but previous studies on cytoplasmic ferritin raise the possibility that it prevents damage to cellular components from “oxidative stress” by sequestering iron and lowering the concentration of active oxygen species (AOS) It remains to be tested whether the nuclear ferritin prevents oxidative damage, we find this an attractive possibility since the corneal epithelium is transparent and is constantly exposed to AOS-generating UV light (see “Discussion”)
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