Basic Properties of the p38 Signaling Pathway in Response to Hyperosmotic Shock
Ben Messaoud, Nabil (Universitat Autònoma de Barcelona. Institut de Neurociències)
Katzarova, Ilina (Universitat Autònoma de Barcelona. Institut de Neurociències)
López Blanco, José Manuel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Fecha:	2015
Resumen:	Some properties of signaling systems, like ultrasensitivity, hysteresis (a form of biochemical memory), and all-or-none responses at a single cell level, are important to understand the regulation of irreversible processes. Xenopus oocytes are a suitable cell model to study these properties. The p38 MAPK (mitogen-activated protein kinase) pathway is activated by different stress stimuli, including osmostress, and regulates multiple biological processes, from immune response to cell cycle. Recently, we have reported that activation of p38 and JNK regulate osmostress-induced apoptosis in Xenopus oocytes and that sustained activation of p38 accelerates cytochrome c release and caspase-3 activation. However, the signaling properties of p38 in response to hyperosmotic shock have not been studied. Here we show, using Xenopus oocytes as a cell model, that hyperosmotic shock activates the p38 signaling pathway with an ultrasensitive and bimodal response in a time-dependent manner, and with low hysteresis. At a single cell level, p38 activation is not well correlated with cytochrome c release 2 h after hyperosmotic shock, but a good correlation is observed at 4 h after treatment. Interestingly, cytochrome c microinjection induces p38 phosphorylationthrough caspase-3 activation, and caspase inhibition reduces p38 activation induced by osmostress, indicating that a positive feedback loop is engaged by hyperosmotic shock. To know the properties of the stress protein kinases activated by hyperosmotic shock will facilitate the design of computational models to predict cellular responses in human diseases caused by perturbations in fluid osmolarity.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Xenopus oocytes ; Oocytes ; Phosphorylation ; Stress signaling cascade ; Apoptosis ; MAPK signaling cascades ; Osmotic shock ; Protein kinases
Publicado en:	PloS one, Vol. 10, Num. 9 (September 2015) , p. 1-15, ISSN 1932-6203

DOI: 10.1371/journal.pone.0135249
PMID: 26335493

15 p, 2.0 MB

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