title: Cleavage of bleomycin hydrolase by caspase-3 during apoptosis.
abstract: Bleomycin hydrolase (BLH) affects bleomycin chemotherapy through inactivation of bleomycin with deamination. As a neutral cysteine protease, it also plays various roles in physiological conditions and diseases. However, its mechanism of degradation remains unclear. In the present study, we showed that the levels of BLH were significantly reduced during apoptosis induced by the antitumor agents bleomycin, etoposide and hydroxycamptothecin, and inhibited by the caspase inhibitors Q-VD-oph and Z-DEVD-FMK. Furthermore, the caspase-dependent cleavage of BLH was confirmed by cleavage of partly-purified human BLH with caspase-3 and caspase-9 in vitro. The stability of BLH at normal culture conditions was analyzed with the protein synthesis inhibitor cycloheximide and the proteasome inhibitor MG132. BLH was degraded at a rate lower than that of cyclin D1. This is the first report to demonstrate that BLH is cleaved by caspase-3 during apoptosis.
authors.affiliation: Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.forename: Qiyang
authors.initials: Q
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001761:Bleomycin / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D001761:Bleomycin; D019938:Cyclin D1; D005047:Etoposide; D053148:Caspase 3; D053453:Caspase 9; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase