Characterization and accumulation of ferritin in hepatocyte nuclei of mice with iron overload

✍ Scribed by Andrew G. Smith; Philip Carthew; Jean E. Francis; Richard E. Edwards; David Dinsdale

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 773 KB
• Volume: 12
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840120622

✦ Synopsis

After a single subcutaneous dose of iron-dextran (600 mg of ironkg), iron overload developed in CS7BL/lOScSn 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 pm in diameter, occupying >25% of the nuclear volume. The presence of iron in the inclusions was confumed 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 w k 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. (HEPA-