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Characterization and accumulation of ferritin in hepatocyte nuclei of mice with iron overload
Author(s) -
Smith Andrew G.,
Carthew Philip,
Francis Jean E.,
Edwards Richard E.,
Dinsdale David
Publication year - 1990
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840120622
Subject(s) - ferritin , nucleoplasm , chemistry , hepatocyte , cytoplasm , biophysics , radiochemistry , microanalysis , biochemistry , biology , in vitro , nucleolus , organic chemistry
After a single subcutaneous dose of iron‐dextran (600 mg of iron/kg), iron overload developed in C57BL/10ScSn mice. At 4, 24 and 78 wk liver nonheme iron concentrations were 67‐, 42‐ and 21‐fold higher than controls, respectively. Much of the iron was in macrophages, but hepatocytes were also strongly positive for Perls' stainable iron. One feature was the development of iron‐positive nuclear inclusions in hepatocytes. After a delay of at least 8 wk when no stainable iron was evident, a maximum of 37% of periportal hepatocytes contained inclusions by 24 wk. Although this proportion remained constant for the remainder of the study, the size of the inclusions (which were not membrane‐limited) increased to > 3 μm in diameter, occupying > 25% of the nuclear volume. The presence of iron in the inclusions was confirmed by energy dispersive x‐ray microanalysis. Immunocytochemical studies showed that the iron was present as aggregates of ferritin. Quantitation of nonaggregated ferritin molecules by image analyses after electron microscopy demonstrated that within 4 wk ferritin levels in cytoplasm and nucleoplasm had greatly increased but that there was a concentration gradient of approximately one order of magnitude across the nuclear envelope. These findings are consistent with the hypothesis that in iron‐loaded mouse hepatocytes there is a slow passage of ferritin‐molecules through the nuclear pores; the gradient is maintained by the continual aggregation of ferritin within the nucleus. Intranuclear ferritin may provide a source of iron for catalyzing hydroxyl radical formation in nuclei during some toxic, carcinogenic and aging processes. (HEPATOLOGY 1990;12:1399–1405).