Lens epithelial cells synthesize and secrete ceruloplasmin: effects of ceruloplasmin and transferrin on iron efflux and intracellular iron dynamics.
Although an essential nutrient, iron can catalyze damaging free radical reactions. Therefore elaborate mechanisms have evolved to carefully regulate iron metabolism. Ceruloplasmin, a protein with ferroxidase activity, and transferrin, an iron binding protein have important roles in maintaining iron homeostasis in cells. Since oxidative damage is a hallmark of cataractogenesis, it is essential to determine iron's role in lenticular physiology and pathology. In the current study of lens epithelial cells, the effects of ceruloplasmin and transferrin on intracellular distribution and efflux of iron were determined. Both ceruloplasmin and transferrin increased iron efflux from these cells and their effects were additive. Ceruloplasmin had significant effects on extracellular iron distribution only in cases of iron overload. Surprisingly, both transferrin and ceruloplasmin had significant effects on intracellular iron distribution. Under physiological conditions, ceruloplasmin increased iron incorporation into the storage protein, ferritin. Under conditions of iron overload, it decreased iron incorporation into ferritin, which is consistent with increased efflux of iron. Measurements of an intracellular chelatable iron pool indicated that both transferrin and ceruloplasmin increased the size of this pool at 24 h, but these increases had different downstream effects. Finally, lens epithelial cells made and secreted transferrin and ceruloplasmin. These results indicate an important role for these proteins in iron metabolism in the lens.
Harned
J
J
Department of Molecular Biomedical Sciences, North Carolina State University, 4700 Hillsborough Street, Raleigh, 27606, USA.
Fleisher
L N
LN
McGahan
M C
MC
D000818:Animals; D002570:Ceruloplasmin / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology; D017077:Culture Media, Conditioned; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007903:Lens Capsule, Crystalline / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D046509:Tissue Culture Techniques; D014168:Transferrin / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology
D017077:Culture Media, Conditioned; D014168:Transferrin; D005293:Ferritins; D007501:Iron; D002570:Ceruloplasmin