Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Bleomycin hydrolase activity in pulmonary cells.

J S Lazo, W W Merrill, E T Pham

    The Journal of Pharmacology and Experimental Therapeutics
    |December 1, 1984
    PubMed
    Summary

    Bleomycin hydrolase metabolizes bleomycin (BLM) A2 into a less toxic form. Lung cells, particularly pulmonary endothelium and fibroblasts, show varied activity, potentially influencing BLM lung toxicity.

    Related Concept Videos

    You might also read

    Related Articles

    Articles linked to this work by shared authors, journal, and citation graph.

    Sort by
    Same author

    Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up.

    Annals of oncology : official journal of the European Society for Medical Oncology·2018
    Same author

    Mutation profiles in early-stage lung squamous cell carcinoma with clinical follow-up and correlation with markers of immune function.

    Annals of oncology : official journal of the European Society for Medical Oncology·2017
    Same author

    Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up.

    Annals of oncology : official journal of the European Society for Medical Oncology·2016
    Same author

    Butyrylcholinesterase: an enzyme antidote for cocaine intoxication.

    Addiction biology·2016
    Same author

    Clinical outcomes in elderly patients with advanced non-small cell lung cancer: results from ARIES, a bevacizumab observational cohort study.

    Clinical oncology (Royal College of Radiologists (Great Britain))·2015
    Same author

    Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial.

    Annals of oncology : official journal of the European Society for Medical Oncology·2012

    Area of Science:

    • Pulmonary Pharmacology
    • Cellular Metabolism
    • Drug Metabolism

    Background:

    • Bleomycin (BLM) is an anticancer drug known for its pulmonary toxicity.
    • The enzyme bleomycin hydrolase (BLMH) is implicated in BLM metabolism.
    • Understanding the cellular distribution of BLMH is crucial for predicting BLM-induced lung injury.

    Purpose of the Study:

    • To investigate the activity and distribution of bleomycin hydrolase in various pulmonary cell types.
    • To determine the role of cellular BLMH levels in bleomycin A2 metabolism.
    • To explore the implications of BLMH heterogeneity for BLM lung toxicity.

    Main Methods:

    • High-pressure liquid chromatography (HPLC) was used to assay bleomycin A2 metabolism.
    • Cytosol fractions from isolated and cultured pulmonary cells (macrophages, fibroblasts, endothelial cells, pneumocytes) were analyzed.

    Related Experiment Videos

  • Kinetic parameters (Km, Vmax) of BLMH activity were determined in cultured rabbit pulmonary fibroblasts.

    • Main Results:

    • Bleomycin A2 was converted to its less toxic desamido metabolite by BLMH in macrophages, fibroblasts, and endothelial cells.
    • Pulmonary fibroblasts and endothelial cells exhibited 3-5 times higher BLMH activity per cell compared to macrophages.
    • Freshly isolated type II pneumocytes and cultured bovine pulmonary artery endothelial cells showed undetectable BLMH activity.
    • BLMH activity in rabbit pulmonary fibroblasts was stable in culture over multiple passages and cell densities.

    Conclusions:

    • Significant heterogeneity exists in the cellular distribution of bleomycin hydrolase activity within the lungs.
    • High BLMH activity in pulmonary endothelium and fibroblasts may play a protective role against bleomycin-induced lung toxicity.
    • Species and cell-type-specific differences in BLMH expression could influence individual susceptibility to bleomycin.