ATP IN IRON OVERLOAD-INDUCED INTRACELLULAR CALCIUM CHANGES

The cellular iron uptake from low molecular weight iron complexes (fer ric citrate, ferric lactate and ferric ATP complex) is concentration-d ependent, and only a small part of the iron penetrates the cell as sho wn by deferoxamine treatment. A threshold of iron concentration in the cell must be reached for the iron complex-induced increase of cellula r Ca2+-uptake. ATP seems to play a key role in an iron translocation t hat enhances the effects of the iron complexes. A non-specific and com petitive iron-binding by proteins seems to act as a buffer system that reduces the iron overload effects. Calcium channel blockers have no e ffects on the iron complex-cell interaction or iron-induced Ca2+-uptak e modification. An iron complex concentration-dependent inhibition of the CaATPase activity, and its consequent Ca2+-extrusion impairment ap pear as the likely cause of calcium overload. The relevance of these f indings in iron overload-induced pathologies is discussed.