Does the haemosiderin iron core determine its potential for chelation and the development of iron-induced tissue damage?
Haemosiderin, the major iron storage protein in tissues of iron-loaded tissues shows heterogeneity with respect to both its iron mineralisation product and associated protein. Such mineralisation products have been characterised by a variety of physical techniques including Mössbauer spectroscopy, electron diffraction and EXAFS, and are closely related to the mineral ferrihydrite. A wide range of iron chelators are being developed for the treatment of abnormal haemoglobinopathies, predominantly beta-thalassaemia, which may show greater chelator efficacy for particular mineralisation products of haemosiderin. Even though the tissue iron loadings achieved in different iron-loading syndromes are similar, e.g. naturally occurring iron loading, genetic haemochromatosis and thalassaemia, it is clear that the iron loading in thalassaemic causes extensive damage. The explanation for this could relate to the distribution of iron within different cell types, predominantly reticuloendothelial, its rate of deposition and the mineralisation product of its haemosiderin iron core, goethite.
Ward
R J
RJ
Unité de Biochemie, Catholique Université de Louvain, Louvain-la-Neuve, Belgium.
Legssyer
R
R
Henry
C
C
Crichton
R R
RR
D000818:Animals; D002614:Chelating Agents; D018360:Crystallography, X-Ray; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism*; D006485:Hemosiderin / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000032:analysis* / Q000378:metabolism; D015204:Spectroscopy, Mossbauer; D013154:Spleen / Q000378:metabolism; D013789:Thalassemia / Q000235:genetics / Q000378:metabolism; D014714:Vertebrates
D002614:Chelating Agents; D006485:Hemosiderin; D007501:Iron