ATP in iron overload-induced intracellular calcium changes.
The cellular iron uptake from low molecular weight iron complexes (ferric citrate, ferric lactate and ferric ATP complex) is concentration-dependent, and only a small part of the iron penetrates the cell as shown by deferoxamine treatment. A threshold of iron concentration in the cell must be reached for the iron complex-induced increase of cellular Ca2+-uptake. ATP seems to play a key role in an iron translocation that enhances the effects of the iron complexes. A non-specific and competitive iron-binding by proteins seems to act as a buffer system that reduces the iron overload effects. Calcium channel blockers have no effects on the iron complex-cell interaction or iron-induced Ca2+-uptake modification. An iron complex concentration-dependent inhibition of the CaATPase activity, and its consequent Ca2+-extrusion impairment appear as the likely cause of calcium overload. The relevance of these findings in iron overload-induced pathologies is discussed.
Anghileri
L J
LJ
Laboratory of Biophysics, Faculty of Medicine, University of Nancy, BP 184, F-54505 Vandoeuvre les Nancy, France.
Thouvenot
P
P
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000378:metabolism / Q000494:pharmacology; D019190:Iron Overload / Q000378:metabolism*; D019344:Lactic Acid / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology
D015220:Calcium Channels; D007502:Iron Chelating Agents; D014268:Trifluoperazine; D019344:Lactic Acid; D007811:Lanthanum; D000255:Adenosine Triphosphate; D012964:Sodium; D007501:Iron; D009543:Nifedipine; D003676:Deferoxamine; D002118:Calcium