title: Palytoxin induces dissociation of HSP 27 oligomers through a p38 protein kinase pathway.
abstract: 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.
authors.affiliation: Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, Via Campi 287, I-41125 Modena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Berni
authors.affiliation: Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, Via Campi 287, I-41125 Modena, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Bellocci
authors.affiliation: Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, Via Campi 287, I-41125 Modena, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Sala
authors.affiliation: Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, Via Campi 287, I-41125 Modena, Italy.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Rossini
mesh_terms: D001704:Biopolymers / Q000378:metabolism*; D004789:Enzyme Activation; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D061986:MCF-7 Cells; D018832:Molecular Chaperones; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D001704:Biopolymers; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D048051:p38 Mitogen-Activated Protein Kinases