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
Data de publicació
2006-03-10ISSN
0021-9258
Resum
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.
Tipus de document
Article
Versió del document
Versió publicada
Llengua
English
Matèries (CDU)
61 - Medicina
Paraules clau
Apoptosi
Cervell -- Malalties
Potassi
Mitocondris
Apoptosis
Cerebro -- Enfermedades
Potasio
Mitocondrias
Apoptosis
Brain -- Diseases
Potassium
Mitochondria
Pàgines
12
Publicat per
Elsevier
Col·lecció
281; 10
Publicat a
Journal of Biological Chemistry
Citació
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 de l'acord de la subvenció
repo/grantAgreement/ES/1PN/SAF2001-1941
Aquest element apareix en la col·lecció o col·leccions següent(s)
- Ciències de la Salut [740]
Drets
Under a Creative Commons license. This is an Open Access article under the CC-BY License.
Excepte que s'indiqui una altra cosa, la llicència de l'ítem es descriu com https://creativecommons.org/licenses/by/4.0/