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Peroxynitrite-induced p38 MAPK pro-apoptotic signaling in enterocytes
- Source :
-
Biochemical & Biophysical Research Communications . Jun2009, p221-225. 5p. - Publication Year :
- 2009
-
Abstract
- Abstract: Enterocyte apoptosis in necrotizing enterocolitis is partly due to the elaboration of toxic intermediates of nitric oxide (NO), such as peroxynitrite (PN). Because p38 mitogen-activated protein kinase (MAPK) and serine–threonine kinase (AKT) are well-characterized pro- and anti-apoptotic mediators, respectively, we hypothesized that PN could induce enterocyte apoptosis via activation of p38 and deactivation of AKT. To test this hypothesis, the rat intestinal cell line, IEC-6, was treated with PN. PN caused phosphorylation of p38, its upstream activator, MKK3/6, and downstream effector, transcription factor ATF-2. PN-induced apoptosis was inhibited by the p38 inhibitor, SB202190, and by p38 siRNA. PN decreased AKT phosphorylation; this effect was abrogated by pre-treatment with SB202190 or p38 siRNA. PN exposure also increased the activity of the protein phosphatase 2A (PP2A). These data demonstrate that PN-mediated apoptosis depends on the p38 pathway and that p38 mediates deactivation of AKT survival pathways possibly by the involvement of PP2A. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 0006291X
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 39776555
- Full Text :
- https://doi.org/10.1016/j.bbrc.2009.04.091