Human bleomycin hydrolase regulates the secretion of amyloid precursor protein.
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, beta amyloid (Abeta). 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 APPalpha/beta products without changing the half-life of cellular APP. We also observed that this increased Abeta secretion was independent of hBH isoforms. Our findings suggest a regulatory role for hBH in APP processing pathways.
Lefterov
I M
IM
Department of Pharmacology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Koldamova
R P
RP
Lazo
J S
JS
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry; D013462:Sulfur Radioisotopes; D014162:Transfection; D014283:Triiodobenzoic Acids / Q000737:chemistry
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007527:Isoenzymes; D013462:Sulfur Radioisotopes; D014283:Triiodobenzoic Acids; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase; C044834:iodixanol