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Potential abnormalities in iron metabolism in hyperlipidemia patient fibroblasts
Author(s) -
Morrison Chevaun,
Sauble Eric N,
Nguyen Annie,
La Alice,
Bach Gideon,
Linder Maria C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.105.4
Subject(s) - endosome , ferritin , iron deficiency , endocytosis , chemistry , metabolism , biochemistry , microbiology and biotechnology , lysosome , cytoplasm , medicine , anemia , endocrinology , biology , cell , enzyme
Mucolipidosis type IV (MLIV) is an autosomal recessive neurodegenerative disorder that results from a mutation in mucolipin 1, a 580 amino acid non‐selective cation channel present on lysosomal membranes. This mutation disrupts sorting, transport and/or fusion of endosomes and lysosomes, and subjects suffer from iron deficiency anemia. To establish whether lysosomal turnover of endogenous ferritin was disrupted, fibroblasts from normal and MLIV subjects were pretreated with 59 Fe‐labeled ferric ammonium citrate (180 uM) for 24h to produce ferritin (Ft) and then with desferioxamine to induce Ft turnover in lysosomes (Kidane et al, Am J Physiol 291: C445, 2006). No defects in Ft turnover and Fe release were observed, as demonstrated with iodixanol density gradients separating cytoplasmic and lysosomes/endosomal Ft and its iron. However, when exogenous (cationized) horse spleen Ft was administered, turnover of this iron was slowed and more was held in lysosomes and endosomes in the case of cells from diseased subjects. Accumulation of cytoplasmic Ft protein (measured by ELISA) was also reduced. We conclude that a reduced rate of processing of iron entering by endocytosis may slow recycling of red cell iron and contribute to the development an iron deficiency‐like anemia. Supported in part by PHS Grant No. RO1 HD 46949.