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Human bleomycin hydrolase regulates the secretion of amyloid precursor protein

Department of Pharmacology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261, USA

²Correspondence: Department of Pharmacology, University of Pittsburgh School of Medicine, Biomedical Science Tower E1340, Pittsburgh, PA 15261, USA. E-mail: lazo+{at}pitt.edu

Human bleomycin hydrolase (hBH) is a neutral cysteine protease genetically associated with increased risk for Alzheimer disease. We show here that ectopic expression of hBH in 293APPwt and CHOAPPsw cells altered the processing of amyloid precursor protein (APP) and increased significantly the release of its proteolytic fragment, ß amyloid (Aß). We also found that hBH interacted and colocalized with APP as determined by subcellular fractionation, in vitro binding assay, and confocal immunolocalization. Metabolic labeling and pulse-chase experiments showed that ectopic hBH expression increased secretion of soluble APP/ß products without changing the half-life of cellular APP. We also observed that this increased Aß secretion was independent of hBH isoforms. Our findings suggest a regulatory role for hBH in APP processing pathways.—Lefterov, I. M., Koldamova, R. P., Lazo, J. S. Human bleomycin hydrolase regulates the secretion of amyloid precursor protein.

Key Words: Alzheimer disease • protease • ß-amyloid

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