Polymorphism of hen egg white lysozyme amyloid fibrils influences the cytotoxicity in LLC-PK1 epithelial kidney cells
| Autor: | Alexandru Filippi, Zuzana Bednarikova, Andrea Antosova, Constanta Ganea, Zuzana Gazova, Erna Demjen, Katarina Siposova, Jozef Marek, Maria-Magdalena Mocanu, Irina Baran |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Amyloid
Programmed cell death Apoptosis macromolecular substances Biology Kidney Fibril Biochemistry Protein Structure Secondary Necrosis Amyloid disease chemistry.chemical_compound Structural Biology Animals Cytotoxic T cell Cytotoxicity Molecular Biology Cell Proliferation Cytotoxins Cell growth Epithelial Cells General Medicine Hydrogen-Ion Concentration chemistry Biophysics Muramidase Protein Multimerization Lysozyme |
| Zdroj: | International Journal of Biological Macromolecules. 65:176-187 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2014.01.030 |
| Popis: | The polymorphism of amyloid fibrils is potentially crucial as it may underlie the natural variability of amyloid diseases and could be important in developing a fuller understanding of the molecular basis of protein deposition disorders. This study examines morphological differences in lysozyme fibrils and the implications of these differences in terms of cytotoxicity. The structural characteristics of amyloid fibrils formed under two different experimental conditions (acidic and neutral) were evaluated using spectroscopic methods, atomic force microscopy and image analysis. Growth curves and apoptotic/necrotic assays were used to determine the cytotoxic effect of fibrils on the LLC-PK1 renal cells. The results reveal that both types of mature lysozyme amyloid fibrils are actively involved in the cytotoxic process, however each exhibit different levels of cytotoxicity. Fibrils formed at acidic pH affect cell growth in a dose-dependent manner, but a threshold-dependent inhibition of cell growth was observed in the case of lysozyme fibrils prepared at neutral pH. Experiments examining the mechanism of the cell death suggest that both types of mature lysozyme fibrils trigger late apoptosis/necrosis at different fibril concentrations. Our findings clearly indicate that the intrinsic differences between amyloid fibrils due to their polymorphism result in different degrees of cytotoxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect