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Neurodegenerative effects of azithromycin in differentiated PC12 cells.

Azithromycin is a widely used macrolide antibiotic with sustained and high tissue penetration and intracellular accumulation. While short-term exposure to low-dose azithromycin is usually well tolerated, prolonged treatment can lead to unwanted neurological effects like paresthesia and hearing loss. However, the mechanism causing neurodegeneration is still unknown. Here, we show that even low therapeutically relevant azithromycin concentrations like 1µg/ml decreased cell viability by 15% and induced neurite loss of 47% after 96h in differentiated PC12 cells, which are a well-established model system for neuronal cells. When higher concentrations were used, the drug-induced effects occurred earlier and were more pronounced. Thereby, azithromycin altered tropomyosin-related kinase A (TrkA) signaling and attenuated protein kinase B (Akt) activity, which subsequently induced autophagy. Simultaneously, the antibiotic impaired lysosomal functions by blocking the autophagic flux, and this concurrence reduced cell viability. In good agreement with reversible effects observed in patients, PC12 cells could completely recover if azithromycin was removed after 24h. In addition, the detrimental effects of azithromycin were limited to differentiated cells, as confirmed in the human neuronal model cell line SH-SY5Y. Thus, azithromycin alters cell surface receptor signaling and autophagy in neuronal cells, but does not automatically induce irreversible damage when used in low concentrations and for a short time.

Pubmed ID: 28479141 RIS Download

Mesh terms: Animals | Autophagy | Azithromycin | Cell Differentiation | Cell Line, Tumor | Cell Survival | Dose-Response Relationship, Drug | Humans | JNK Mitogen-Activated Protein Kinases | Mitogen-Activated Protein Kinase 1 | Mitogen-Activated Protein Kinase 3 | Nerve Growth Factor | Neurites | Neurons | PC12 Cells | Proto-Oncogene Proteins c-akt | Rats | Receptor, Nerve Growth Factor | Signal Transduction | Time Factors

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Journal of Comparative Neurology Antibody database

The JCN antibody database is a listing of all antibodies used in JCN papers from 2006 onward. The catalog numbers and vendor information is included for all antibodies listed, and with a new collaboration with NIF''''s AntibodyRegistry, a unique identifier is also listed for each antibody. The Journal of Comparative Neurology requires rigorous characterization for all antibodies that are used in JCN papers. The antibodies in the The Journal of Comparative Neurology antibody database have in nearly all cases been described and characterized adequately according to the provided guidelines. This information can be used to identify a particular target immunohistochemically or to design an experiment using the antibody information. If you are looking for an antibody to identify a particular target immunohistochemically, this list is a good place to begin your search. We suggest you then look up the paper in which the antibody was used, to make sure that it will meet your needs and to verify its characterization. (The characterization of antibodies in JCN papers often goes well beyond the material published by the manufacturer, so that examining this information before you order an antibody can be very useful.) While we do not guarantee that these antibodies will identify only the intended target (that is a function of the actual experiment and controls), this is the most carefully verified list of antibodies that we are aware of, and we wanted to share this resource with our readers and authors.

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