NUCLEAR FERRITIN PROTECTS DNA FROM UV DAMAGE IN CORNEAL EPITHELIAL-CELLS

Previously, we identified the heavy chain of ferritin as a development ally regulated nuclear protein of embryonic chicken corneal epithelial cells. The nuclear ferritin is assembled into a supramolecular form i ndistinguishable from the cytoplasmic form of ferritin found in other cell types and thus most likely has iron-sequestering capabilities. Fr ee iron, via the Fenton reaction, is known to exacerbate UV-induced an d other oxidative damage to cellular components, including DNA. Since corneal epithelial cells are constantly exposed to UV light, we hypoth esized that the nuclear ferritin might protect the DNA of these cells from free radical damage. To test this possibility, primary cultures o f cells from corneal epithelium and stroma, and from skin epithelium a nd stroma, were UV irradiated, and DNA strand breaks were detected by an in situ 3'-end labeling method. Corneal epithelial cells without nu clear ferritin were also examined. We observed that the corneal epithe lial cells with nuclear ferritin had significantly less DNA breakage t han other cell types examined. Furthermore, increasing the iron concen tration of the culture medium exacerbated the generation of UV-induced DNA strand breaks in corneal and skin fibroblasts, but not in the cor neal epithelial cells. Most convincingly, corneal epithelial cells in which the expression of nuclear ferritin was inhibited became much mor e susceptible to UV-induced DNA damage. Therefore, it seems that corne al epithelial cells have evolved a novel, nuclear ferritin-based mecha nism for protecting their DNA against UV damage.