ABSTRACT
Marine microbial enzyme technologies have progressed significantly in the last few decades for different applications. Among the various microorganisms, marine actinobacterial enzymes have significant active properties, which could allow them to be biocatalysts with tremendous bioactive metabolites. Moreover, marine actinobacteria have been considered as biofactories, since their enzymes fulfill biomedical and industrial needs. In this chapter, the marine actinobacteria and their enzymes' uses in biological activities and biomedical applications are described.
Subject(s)
Actinobacteria/enzymology , Aquatic Organisms/enzymology , Enzyme Therapy , Anti-HIV Agents , Anti-Infective Agents , Antineoplastic Agents , Antioxidants , Asparaginase/therapeutic use , Cholesterol Oxidase/therapeutic use , Laccase/therapeutic useABSTRACT
Cholesterol oxidase (COD), an enzyme catalyzing the oxidation of cholesterol, has been applied to track the distribution of membrane cholesterol. Little investigations about the effect of COD on tumor cells have been performed. In the present study, we provided evidence that COD from Bordetella species (COD-B), induced apoptosis of lung cancer cells in vitro and in vivo. COD-B treatment inhibited Akt and ERK1/2 phosphorylation in dose- and time-dependent manner, which was not reversed and was even aggravated by cholesterol addition. Further investigation indicated that COD-B treatment promoted the generation of reactive oxygen species (ROS) and that cholesterol addition further elevated ROS levels. Moreover, COD-B treatment resulted in JNK and p38 phosphorylation, downregulation of Bcl-2, upregulation of Bax, activated caspase-3 and cytochrome C release, which likely responded to freshly produced hydrogen peroxide that accompanied cholesterol oxidation. Catalase pretreatment could only partially prevent COD-B-induced events, suggesting that catalase inhibited H2O2-induced signal transduction but had little effect on signal pathways involved in cholesterol depletion. Our results demonstrated that COD-B led to irreversible cell apoptosis by decreasing cholesterol content and increasing ROS level. In addition, COD-B may be a promising candidate for a novel anti-tumor therapy.
Subject(s)
Bacterial Proteins/metabolism , Bordetella/enzymology , Cholesterol Oxidase/metabolism , Cholesterol/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Animals , Apoptosis/drug effects , Bacterial Proteins/chemistry , Bacterial Proteins/therapeutic use , Caspase 3/metabolism , Catalase/metabolism , Cell Line, Tumor , Cholesterol/analysis , Cholesterol/chemistry , Cholesterol Oxidase/chemistry , Cholesterol Oxidase/therapeutic use , Down-Regulation/drug effects , Humans , Hydrogen Peroxide/toxicity , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Oxidation-Reduction , Phosphorylation/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Up-Regulation/drug effectsSubject(s)
3-Hydroxysteroid Dehydrogenases/therapeutic use , Cholesterol Oxidase/therapeutic use , Hypercholesterolemia/drug therapy , Streptomyces/enzymology , Animals , Cholestenones/blood , Cholesterol/blood , Drug Evaluation, Preclinical , Hypercholesterolemia/blood , In Vitro Techniques , Rabbits , Time FactorsABSTRACT
Cholesterol oxidase (3 beta-hydrosteroid oxidase), isolated from Actinomyces lavendulae, oxidized unesterified cholesterol in rabbit blood serum without detergents in vitro. Intravenous administration of the enzyme into hypercholesterolemic rabbits at a dose of 0.5-2.0 un/kg decrease distinctly the cholesterol content in blood. The rate of the decrease depended on the dose of the preparation. Acute toxicity of the cholesterol oxidase preparations for mice correlated with the degree of purification of the enzyme. Cholesterol oxidase from Act. lavendulae may be considered as a potential hypocholesterolemic drug.
