N-methyl-D-aspartate blocks activation of JNK and mitochondrial apoptotic pathway induced by potassium deprivation in cerebellar granule cells
Xifró Collsamata, Francesc Xavier (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Falluel-Morel, Anthony (University of Rouen)
Miñano Molina, Alfredo Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)
Aubert, Nicolas (University of Rouen)
Fadó, Rut (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Malagelada, Cristina (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Vaudry, David (University of Rouen)
Gonzalez, Bruno (University of Rouen)
Rodríguez Álvarez, José (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2006
Abstract:	During the postnatal development of cerebellum, lack of excitatory innervation from the mossy fibers results in cerebellar granule cell (CGC) apoptosis during the migration of the cells toward the internal granule cell layer. Accordingly, CGCs die by apoptosis when cultured in physiological KCl concentrations (5 mM; K5), and they survive in the presence of depolarizing conditions such as high KCl concentration (25 mM; K25) or N-methyl-D-aspartate (NMDA). We have recently shown that NMDA is able to exert a long lasting neuroprotective effect when added to immature (2 days in vitro) CGC cultures by inhibition of caspase-3 activity. Here we show that NMDA- and K25-mediated neuroprotection is associated with an increase in the levels of Bcl-2, an inhibition of K5-mediated increase in Bax, and the inhibition of the release of apoptogenic factors from mitochondria such as Smac/DIABLO and cytochrome c. Moreover, we have shown that similar effects are observed when c-Jun N-terminal kinases (JNKs) are inhibited and that treatment of CGC cultures with NMDA blocks K5-mediated JNK activation. These results allow us to postulate that the inhibition of JNK-mediated release of apoptogenic factors from mitochondria is involved in the NMDA protection from K5-mediated apoptosis of CGCs.
Grants:	Ministerio de Ciencia y Tecnología SAF2001-1941
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Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Journal of biological chemistry, Vol. 281, Num. 10 (March 2006) , p. 6801-6812, ISSN 1083-351X

DOI: 10.1074/jbc.M504571200

12 p, 1.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles