title: Evidence that the ubiquitin proteolytic pathway is involved in the degradation of precipitated globin chains in thalassaemia.
abstract: Ultrastructural immunocytochemical studies were performed on sections of bone marrow from three patients with beta-thalassaemia major and two patients with haemoglobin H (HbH) disease. Some sections were reacted with either a polyclonal or a monoclonal anti-human-ubiquitin antibody and the reaction visualized using a gold-labelled secondary antibody. The inclusions of precipitated globin chains found within the erythropoietic cells of all five patients reacted much more strongly than the surrounding inclusion-free cytoplasm with both of the anti-ubiquitin antibodies, indicating that the precipitated globin chains were ubiquitinated. A non-specific reaction between the anti-ubiquitin antibodies and the inclusions was excluded by demonstrating that various other antibodies, including a polyclonal anti-human cathepsin D antibody, did not react with the inclusions. The data suggest that the ubiquitin proteolytic pathway is involved in the degradation of precipitated globin chains in alpha- and beta-thalassaemia.
authors.affiliation: Department of Haematology, Imperial College School of Medicine, St Mary's Hospital, London.
authors.forename: S N
authors.initials: SN
authors.lastname: Wickramasinghe
authors.forename: M J
authors.initials: MJ
authors.lastname: Lee
mesh_terms: D002402:Cathepsin D / Q000378:metabolism; D005914:Globins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D014452:Ubiquitins / Q000378:metabolism*; D017086:beta-Thalassemia / Q000378:metabolism*
chemical_list: D014452:Ubiquitins; D005914:Globins; D002402:Cathepsin D