Evidence for a low km transporter for non-transferrin-bound iron in
isolated rat hepatocytes.
Barisani, Donatella, Carl L. Berg, Marianne Wessling-Resnick, and John
L. Gollan.
Gastroenterology Division, Brigham and Women's Hospital, Harvard
Medical School, Boston, MA; Cattedra di Gastroenterologia, IRCCS -
Ospedale Maggiore, Milan, Italy; Harvard School of Public Health,
Boston, MA
APStracts 2:0086G, 1995.
Non-transferrin-bound iron (NTBI) plays an important role in the
hepatocellular injury induced by iron overload. However, the
mechanism responsible for NTBI uptake into hepatocytes remains poorly
defined. The purpose of this study was to define the kinetics of NTBI
uptake by isolated rat hepatocytes, and to characterize the uptake
process. Non-transferrin-bound iron uptake was time- and temperature
-dependent, exhibited a Km of 1.25 [mu]M and Vmax of 241 pmol/106
cells min, and 55Fe was incorporated in part into intracellular
ferritin. Uptake was Ca2+- dependent, exhibiting 15% and 80% of
maximal uptake in the presence of 0.6 and 0.75 mM CaCl2,
respectively. The putative NTBI transporter was highly specific;
divalent (Zn2+, Mn2+, Cd2+, Co2+) or trivalent (La3+) cations did not
inhibit Fe3+ uptake. Reduction from Fe3+ to Fe2+ was not essential
for uptake or the process occurred deep within the membrane bilayer,
since the Fe2+ chelator ferrozine, did not influence 55Fe uptake.
These data provide evidence for a low Km plasma membrane transporter
for NTBI, which should be functional at physiologic serum
concentrations and saturated in iron overload diseases, such as
hemochromatosis.
Received 24 October 1994; accepted in final form 27 April 1995.
APS Manuscript Number G427-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.