Palytoxin Induces Dissociation of HSP 27 Oligomers through a p38 Protein Kinase Pathway
| Autor: | Mirella Bellocci, Gian Paolo Rossini, Gian Luca Sala, Chiara Berni |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
MAPK/ERK pathway
education.field_of_study MAPKAPK2 p38 mitogen-activated protein kinases Population HSP27 Heat-Shock Proteins General Medicine Biology Toxicology p38 Mitogen-Activated Protein Kinases Cell biology Enzyme Activation chemistry.chemical_compound Biopolymers chemistry Palytoxin Heat shock protein MCF-7 Cells Humans Phosphorylation education Protein kinase A Heat-Shock Proteins Molecular Chaperones |
| Zdroj: | Chemical Research in Toxicology. 28:752-764 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx500511q |
| Popis: | Palytoxin (PlTX) induces a stress response in MCF-7 cells that involves the phosphorylation of HSP 27 at serines 15, 78, and 82 by an as yet undetermined mechanism. We have studied the involvement of major groups of the mitogen-activated protein kinase (MAPK) family in this molecular response and focused our analyses on the ERK1/2, JNK, p38 protein kinase (p38K), and ERK5 pathways. The results show that PlTX induces the activation of JNK and p38 kinase but not ERK1/2 and 5 in MCF-7 cells. Through the use of protein kinase inhibitors, we established that blocking p38K, but not JNK, prevents the phosphorylation of HSP 27 induced by PlTX and that MAPKAPK2 participates in the response induced by the toxin under our experimental conditions. The cell death response induced by PlTX was inhibited by preventing JNK phosphorylation but not by blocking p38K/MAPKAPK2 and HSP 27 phosphorylation. Sucrose density gradient centrifugation revealed that MCF-7 cell extracts contain a heterodisperse population of HSP 27, including oligomers and smaller forms. Treating MCF-7 cells with PlTX caused the dissociation of HSP 27 oligomers, and using inhibitors of the JNK and p38K pathways showed that the dissociation of HSP 27 oligomers induced by PlTX involves a p38K-dependent process. We conclude that the changes induced by PlTX in the HSP 27 stress response protein system proceed through a molecular mechanism involving the activation of the p38 kinase pathway and its substrate, MAPKAK2, leading to dissociation of HSP 27 oligomers and the stabilization of a cellular pool of monomers phosphorylated at serines 15, 78 and 82, which could play a protective role against the death response induced by PlTX. |
| Databáze: | OpenAIRE |
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