Regulation of Hfe by stress factors in BV-2 cells.

Mutations in the Hfe gene can be associated with the iron overload disorder known as hemochromatosis. A number of recent studies suggest that carrying an Hfe mutation is a risk factor or genetic modifier for Alzheimer's disease (AD). In AD, Hfe protein expression is induced on cells associated with neuritic plaques and on neurons in the periplaque area. In this study, the factors that may be responsible for induction of Hfe in AD brain were determined using BV-2 cells. Hfe expression was induced by serum deprivation, menadione and beta-amyloid. The labile iron pool was consistently decreased when Hfe expression increased. However, the changes in expression of Hfe appeared independent of the expression of transferrin receptor and ferritin. These data provide insight into the induction of Hfe in AD and indicate that Hfe expression may be a protective function to limit cellular iron exposure during cell stress. These results are the first in a series of studies to understand how mutations in Hfe can be a risk factor for AD.