Valosin containing protein (VCP) interacts with macrolide antibiotics without mediating their anti-inflammatory activities
| Autor: | Sulejman Alihodžić, Denis Polančec, Marjorie A. Smith, Ivica Malnar, Vesna Eraković Haber, Michael Lee, Krunoslav Nujić, Daniela Belamarić, Linda Tomaskovic, Klaus Schneider |
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| Rok vydání: | 2011 |
| Předmět: |
Proteomics
medicine.drug_class Valosin-containing protein Anti-Inflammatory Agents Cell Cycle Proteins Biology Azithromycin Macrolide Antibiotics Cell Line Mice Affinity chromatography In vivo Valosin Containing Protein Clarithromycin medicine Gene silencing Animals Humans Gene Silencing Pharmacology Adenosine Triphosphatases Reproducibility of Results In vitro Anti-Bacterial Agents macrolide chemical proteomics target identification valosin containing protein inflammation Biochemistry Cell culture Drug Design biology.protein Protein Binding |
| Zdroj: | European journal of pharmacology. 677(1-3) |
| ISSN: | 1879-0712 |
| Popis: | In addition to antibacterial activity, some macrolide antibiotics, such as azithromycin and clarithromycin, also exhibit anti- inflammatory properties in vitro and in vivo, although the targets and mechanism(s) of action remain unknown. The aim of the present study was to identify protein targets of azithromycin and clarithromycin which could potentially explain their anti-inflammatory effects. Using chemical proteomics approach, based on compound-immobilized affinity chromatography, valosin containing protein (VCP) was identified as a potential target of the macrolides. Validation studies confirmed the interaction of macrolides and VCP and gave some structural characteristics of this interaction. Cell based assays however, including the use of gene silencing and the study of VCP specific cellular functions in J774.A1 (murine macrophage) and IB3-1 (human cystic fibrotic epithelial) cell lines, failed to confirm an association between the binding of the macrolides to VCP and anti-inflammatory effects. These findings suggest the absence of an abundant high affinity protein target and the potential involvement of other biological molecules in the anti-inflammatory activity of macrolides. |
| Databáze: | OpenAIRE |
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