The labile iron pool of hepatocytes in chronic and acute iron overload and chelator-induced iron deprivation

Abstract

Background : The cytosolic labile iron pool (LIP) is a transitory, catalytically active compartment that has been implicated in cell iron homeostasis and in metal-induced cytotoxicity. Aims : We attempted to define LIP levels in living hepatocytes derived from chronic overloaded rats and from normal hepatocytes either acutely loaded with iron or depleted by chelation. Methods : LIP levels were measured in living rat hepatocytes derived from normal and iron-fed rats. Results : Steady-state LIP levels in untreated hepatocytes (∼0.2 μM) were raised by 1.8-fold following iron loading and were reduced by 0.66-fold by short-term chelation treatment. Changes in LIP were accompanied by the corresponding changes in iron-responsive protein (IRP) activity and ferritin levels, that, in rat hepatocytes isolated from chronically loaded animals, raised by ∼19-fold. Conclusions : Whereas ferritin levels provide an index of long-term or cumulative iron loading, LIP measurements provide an “instantaneous” parameter of iron availability within hepatocytes. The latter was associated with the cell chelatable pool in cells derived from normal and iron-loaded animals, both of which showed similar accessibility to iron chelators.