The aminoglycoside G418 hinders de novo prion infection in cultured cells
| Autor: | Gerold Schmitt-Ulms, Mohadeseh Mehrabian, Hamza Arshad, Joel C. Watts, Zaid A.M. Al-Azzawi, Matthew E. C. Bourkas, Zeel Patel |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
PrPSc Proteins
viruses animal diseases Protein aggregation Biochemistry antibiotics Prion Diseases chemistry.chemical_compound Mice 0302 clinical medicine RT-QuIC real-time quaking-induced conversion protein misfolding DAPI diamidino-2-phenylindole Protein Synthesis Inhibitors 0303 health sciences ThT Thioflavin T Neurodegeneration neurodegeneration Transfection TBS Tris buffered saline 3. Good health Cell biology IRES internal ribosome entry site embryonic structures NCAM neural cell adhesion molecule Research Article GPI glycosylphosphatidylinositol MoPrP mouse PrP Prions PBS phosphate-buffered saline Hamster Biology HaPrP hamster PrP Prion Proteins Cell Line protein aggregation prion 03 medical and health sciences Cell Line Tumor medicine PK proteinase K Animals PrPC Proteins DAPI Molecular Biology Selectable marker 030304 developmental biology cell culture PrP prion protein Cell Biology biochemical phenomena metabolism and nutrition medicine.disease nervous system diseases Aminoglycosides chemistry Cell culture Neural cell adhesion molecule Gentamicins 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | The study of prions and the discovery of candidate therapeutics for prion disease have been facilitated by the ability of prions to replicate in cultured cells. Paradigms in which prion proteins from different species are expressed in cells with low or no expression of endogenous prion protein (PrP) have expanded the range of prion strains that can be propagated. In these systems, cells stably expressing a PrP of interest are typically generated via coexpression of a selectable marker and treatment with an antibiotic. Here, we report the unexpected discovery that the aminoglycoside G418 (Geneticin) interferes with the ability of stably transfected cultured cells to become infected with prions. In G418-resistant lines of N2a or CAD5 cells, the presence of G418 reduced levels of protease-resistant PrP following challenge with the RML or 22L strains of mouse prions. G418 also interfered with the infection of cells expressing hamster PrP with the 263K strain of hamster prions. Interestingly, G418 had minimal to no effect on protease-resistant PrP levels in cells with established prion infection, arguing that G418 selectively interferes with de novo prion infection. As G418 treatment had no discernible effect on cellular PrP levels or its localization, this suggests that G418 may specifically target prion assemblies or processes involved in the earliest stages of prion infection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|