101. Differential role of p38 mitogen activated protein kinase for cellular recovery from attack by pore-forming S. aureus alpha-toxin or streptolysin O.
- Author
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Husmann M, Dersch K, Bobkiewicz W, Beckmann E, Veerachato G, and Bhakdi S
- Subjects
- Adenosine Triphosphate metabolism, Bacterial Proteins pharmacology, Cell Membrane Permeability, Cells, Cultured, Enzyme Activation, Hemolysin Proteins, Humans, MAP Kinase Kinase Kinase 5 antagonists & inhibitors, MAP Kinase Kinase Kinase 5 metabolism, Phosphorylation, Protein-Tyrosine Kinases antagonists & inhibitors, Protein-Tyrosine Kinases metabolism, Proto-Oncogene Proteins antagonists & inhibitors, Proto-Oncogene Proteins metabolism, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors, p38 Mitogen-Activated Protein Kinases metabolism, Bacterial Toxins pharmacology, Cell Membrane metabolism, Keratinocytes drug effects, Keratinocytes enzymology, Staphylococcus aureus, Streptolysins pharmacology, p38 Mitogen-Activated Protein Kinases physiology
- Abstract
Following the observation that cells are able to recover from membrane lesions incurred by Staphylococcus aureus alpha-toxin and streptolysin O (SLO), we investigated the role of p38 in this process. p38 phosphorylation occurred in response to attack by both toxins, commencing within minutes after toxin treatment and waning after several hours. While SLO reportedly activates p38 via ASK1 and ROS, we show that this pathway does not play a major role for p38 induction in alpha-toxin-treated cells. Strikingly divergent effects of p38 blockade were noted depending on the toxin employed. In the case of alpha-toxin, inhibition of p38 within the time frame of its activation led to disruption of the recovery process and to cell death. In contrast, blockade of p38 in SLO permeabilized cells did not affect the capacity of the cells to replenish their ATP stores.
- Published
- 2006
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