N-methyl-DD-aspartate blocks activation of JNK and mitochondrial apoptotic pathway induced by potassium deprivation in cerebellar granule cells
Autor/a
Xifró Collsamata, Xavier
Falluel-Morel, Anthony
Miñano Molina, Alfredo Jesús
Aubert, Nicolas
Fadó Andrés, Rut
Malagelada, Cristina
Vaudry, David
Vaudry, Hubert
Gonzalez, Druno
Rodríguez-Álvarez, José
Fecha de publicación
2006-03-10ISSN
0021-9258
Resumen
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.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
Inglés
Materias (CDU)
61 - Medicina
Palabras clave
Apoptosi
Cervell -- Malalties
Potassi
Mitocondris
Apoptosis
Cerebro -- Enfermedades
Potasio
Mitocondrias
Apoptosis
Brain -- Diseases
Potassium
Mitochondria
Páginas
12
Publicado por
Elsevier
Colección
281;10
Publicado en
Journal of Biological Chemistry
Citación
Xifró, Xavier; Falluel-Morel, Anthony; Miñano, Alfredo [et al.]. N-methyl-DD-aspartate blocks activation of JNK and mitochondrial apoptotic pathway induced by potassium deprivation in cerebellar granule cells. Journal of Biological Chemistry, 2006, 281(10), p. 6801-6812. Disponible en: <https://www.sciencedirect.com/science/article/pii/S0021925819580413?via%3Dihub>. Fecha de acceso: 3 may. 2021. DOI: 10.1074/jbc.M504571200
Número del acuerdo de la subvención
repo/grantAgreement/ES/1PN/SAF2001-1941
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