Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bleomycin (BLM) hydrolase inactivates the BLM class of antitumor antibiotics and protects against BLM-induced pulmonary fibrosis. This enzyme is poorly characterized but believed to be an aminopeptidase B. In the present report, both BLM hydrolase and aminopeptidase B from rabbit pulmonary cytosol were retained by arginyl-Sepharose and BLM-Sepharose affinity columns, further suggesting that these two enzymes are similar. When, however, BLM hydrolase was purified over 1800-fold by using our newly developed high-speed liquid chromatography assay for BLM hydrolase coupled with fast protein liquid chromatography, we found that this partially purified BLM hydrolase preparation lacked aminopeptidase B activity. Furthermore, BLM hydrolase was completely separated, by using anion-exchange Mono Q chromatography, from all the aminopeptidases identified in rabbit pulmonary cytosol: one aminopeptidase B, two aminopeptidases N, and one aminopeptidase with both aminopeptidase B and aminopeptidase N activities. Pulmonary BLM hydrolase also had a higher molecular weight than pulmonary aminopeptidase B. In contrast to aminopeptidase B, BLM hydrolase was not activated by NaCl and was much less stable at 4 degrees C. In addition, bestatin was a potent inhibitor of aminopeptidase B but had little effect on BLM hydrolase, while leupeptin was a potent inhibitor of BLM hydrolase but was less effective against aminopeptidase B. Thus, pulmonary BLM hydrolase and aminopeptidase B have affinity for each other's substrate, but they are clearly distinct enzymes on the basis of charge characteristics, molecular weight, stability, and sensitivity to inhibitors and activators.
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PMID:Separation of the protective enzyme bleomycin hydrolase from rabbit pulmonary aminopeptidases. 310 81

Bleomycin hydrolase (BH) is the only known eukaryotic enzyme that inactivates the widely used antineoplastic agent bleomycin (BLM) and is a primary candidate gene for protection against lethal BLM-induced pulmonary fibrosis and for BLM resistance in tumors. Human BH was found to exist as a single gene that was mapped to chromosome 17 using National Institute of General Medical Sciences human/rodent hybrid mapping panels and localized to 17q11.1-11.2 by linkage analysis using the Centre d'Etude du Polymorphisme Humain reference database. The human BH gene consisted of 11 exons ranging in size from 69-198 bp separated by introns of approximately 1 kb, reflecting the archetypal genomic structure of the cysteine protease family. A polymorphic site was identified in the eleventh exon at bp 1450 encoding either valine or isoleucine. These findings provide essential tools required to define the role of BH in BLM-induced pulmonary fibrosis and BLM resistance in tumors.
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PMID:Genomic structure and genetic mapping of the human neutral cysteine protease bleomycin hydrolase. 933 Oct 73