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Role of p38alpha/beta MAP Kinase in Cell Susceptibility to Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B.
- Source :
- Toxins; Jan2017, Vol. 9 Issue 1, p2, 14p
- Publication Year :
- 2017
-
Abstract
- Lethal Toxin from Clostridium sordellii (TcsL), which is casually involved in the toxic shock syndrome and in gas gangrene, enters its target cells by receptor-mediated endocytosis. Inside the cell, TcsL mono-O-glucosylates and thereby inactivates Rac/Cdc42 and Ras subtype GTPases, resulting in actin reorganization and an activation of p38 MAP kinase. While a role of p38 MAP kinase in TcsL-induced cell death is well established, data on a role of p38 MAP kinase in TcsL-induced actin reorganization are not available. In this study, TcsL-induced Rac/Cdc42 glucosylation and actin reorganization are differentially analyzed in p38<subscript>alpha</subscript> -/- MSCV empty vector MEFs and the corresponding cell line with reconstituted p38<subscript>alpha</subscript> expression (p38<subscript>alpha</subscript> -/- MSCV p38<subscript>alpha</subscript> MEFs). Genetic deletion of p38<subscript>alpha</subscript> results in reduced susceptibility of cells to TcsL-induced Rac/Cdc42 glucosylation and actin reorganization. Furthermore, SB203580, a pyridinyl imidazole inhibitor of p38<subscript>alpha/beta</subscript> MAP kinase, also protects cells from TcsL-induced effects in both p38-/- MSCV empty vector MEFs and in p38<subscript>alpha</subscript> -/- MSCV p38<subscript>alpha</subscript> MEFs, suggesting that inhibition of p38<subscript>beta</subscript> contributes to the protective effect of SB203580. In contrast, the effects of the related C. difficile Toxin B are responsive neither to SB203580 treatment nor to p38<subscript>alpha</subscript> deletion. In conclusion, the protective effects of SB203580 and of p38<subscript>alpha</subscript> deletion are likely not based on inhibition of the toxins' glucosyltransferase activity rather than on inhibited endocytic uptake of specifically TcsL into target cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20726651
- Volume :
- 9
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Toxins
- Publication Type :
- Academic Journal
- Accession number :
- 120975152
- Full Text :
- https://doi.org/10.3390/toxins9010002