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


OBJECTIVE
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 ( approximately 0.2 microM) 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 approximately 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.
Zanninelli
Giuliana
G
Department of Biological Chemistry, Institute of Life Science, Hebrew University of Jerusalem, Jerusalem 91120, Israel. gzanninelli@hotmail.com
Loréal
Olivier
O
Brissot
Pierre
P
Konijn
Abraham M
AM
Slotki
Itzchak N
IN
Hider
Robert C
RC
Ioav Cabantchik
Z
Z
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D003600:Cytosol / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D005452:Fluoresceins; D005453:Fluorescence; D022781:Hepatocytes / Q000378:metabolism*; D007501:Iron / Q000493:pharmacokinetics*; D007502:Iron Chelating Agents / Q000494:pharmacology; D000090463:Iron Deficiencies; D019190:Iron Overload / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D005452:Fluoresceins; D007502:Iron Chelating Agents; D005293:Ferritins; D007501:Iron; C007740:fluorexon