LYSOSOME-DEPENDENT CELL DEATH DEFINES SPECIFIC ENDOTHELIAL TOXICITY OF CALCIUM PHOSPHATE BIONS
| Autor: | D. K. Shishkova, E. A. Velikanova, R. A. Mukhamadiyarov, A. E. Yuzhalin, Yu. A. Kudryavtseva, A. N. Popova, D. M. Russakov, A. G. Kutikhin |
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| Jazyk: | ruština |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Сибирский научный медицинский журнал, Vol 39, Iss 4, Pp 12-21 (2019) |
| Druh dokumentu: | article |
| ISSN: | 2410-2512 2410-2520 |
| DOI: | 10.15372/SSMJ20190402 |
| Popis: | Aim of the study was to identify the mechanism of specific endothelial toxicity related to calcium phosphate bions (CPB). Material and methods. CPB and magnesium phosphate bions (MPB) were artificially synthesised through supersaturation of culture medium with respective salts and then added to human endothelial cells (EA.hy 926) and murine endothelial cells (2H-11) to study: 1) spatiotemporal aspects of bion internalisation by means of transmission electron microscopy and confocal microscopy; 2) whether blocking of H+-ATPase by lysosomal inhibitor bafilomycin A1 affects endothelial toxicity of bions; 3) expression of caspase-3 and its substrate poly(ADP-ribose) polymerase (PARP-1). Results. CPB were internalized by endothelial cells as early as 1 h upon their addition and were localized in lysosomes; after 4 h, we detected release of calcium ions (Ca2+) from lysosomes to cytosol accompanied by multifold increase in cleaved caspase 3 and its substrate PARP-1. Bafilomycin A1 rescued endothelial cells from death induced by slightly soluble CPB regardless of exposure time and dose; however, freely soluble MPB did not evince endothelial toxicity regardless of bafilomycin A1 addition. Conclusion. Upon internalization by endothelial cells, CPB cause their death due to dissolution in lysosomes and subsequent release of calcium ions into the cytosol, ultimately leading to cleavage of executioner caspases. MPB lack endothelial toxicity because their dissolution does not lead to release of calcium ions. Therefore, specific endothelial toxicity of CPB is defined by lysosome-dependent cell death. |
| Databáze: | Directory of Open Access Journals |
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