| Autor: |
Daniel R. Neill, Aras Kadioglu, Roman Schoenauer, Eduard B. Babiychuk, Heidi Wolfmeier, Alexander P. Atanassoff, Annette Draeger |
| Jazyk: |
angličtina |
| Předmět: |
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| Zdroj: |
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. (9):2045-2054 |
| ISSN: |
0167-4889 |
| DOI: |
10.1016/j.bbamcr.2014.09.005 |
| Popis: |
Pneumolysin (PLY), a key virulence factor of Streptococcus pneumoniae , permeabilizes eukaryotic cells by forming large trans-membrane pores. PLY imposes a puzzling multitude of diverse, often mutually excluding actions on eukaryotic cells. Whereas cytotoxicity of PLY can be directly attributed to the pore-mediated effects, mechanisms that are responsible for the PLY-induced activation of host cells are poorly understood. We show that PLY pores can be repaired and thereby PLY-induced cell death can be prevented. Pore-induced Ca 2 + entry from the extracellular milieu is of paramount importance for the initiation of plasmalemmal repair. Nevertheless, active Ca 2 + sequestration that prevents excessive Ca 2 + elevation during the execution phase of plasmalemmal repair is of no less importance. The efficacy of plasmalemmal repair does not only define the fate of targeted cells but also intensity, duration and repetitiveness of PLY-induced Ca 2 + signals in cells that were able to survive after PLY attack. Intracellular Ca 2 + dynamics evoked by the combined action of pore formation and their elimination mimic the pattern of receptor-mediated Ca 2 + signaling, which is responsible for the activation of host immune responses. Therefore, we postulate that plasmalemmal repair of PLY pores might provoke cellular responses that are similar to those currently ascribed to the receptor-mediated PLY effects. Our data provide new insights into the understanding of the complexity of cellular non-immune defense responses to a major pneumococcal toxin that plays a critical role in the establishment and the progression of life-threatening diseases. Therapies boosting plasmalemmal repair of host cells and their metabolic fitness might prove beneficial for the treatment of pneumococcal infections. This article is part of a Special Issue entitled: 13th European Symposium on Calcium. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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