INVESTIGADORES
CARUSO Carla Mariana
congresos y reuniones científicas
Título:
Reduced cAMP levels and Akt activation are implicated in the anti-apoptotic actions of mGluR3 agonists in astrocytes
Autor/es:
D. DURAND; L. CARNIGLIA; C. CARUSO; M. LASAGA
Lugar:
Huerta Grande, Cordoba
Reunión:
Congreso; II Reunion Conjunta de Neurociencias; 2010
Institución organizadora:
Sociedad Argentina de Investigacion en Neurociencias
Resumen:
Metabotropic glutamate receptors (mGluR) are implicated
in neuroplasticity and neuroprotection. We have previously shown that mGluR3
activation prevents NO-induced astrocyte death, by modulating levels of
apoptotic mitochondrial pathway mediators. Since mGluR3 activation inhibits
adenylate cyclase and induces Akt activation, we studied these pathways. A
non-hydrolyzable analog of cAMP, dibutyryl-cAMP and an Akt1/2 inhibitor both
abolished the anti-apoptotic effect of the mGluR3 agonists LY379268 or LY404039
on cultured astrocytes exposed to NO (p<0.001 vs. NO+LY). However, a cGMP
analog, 8Br-cGMP, did not modify the effect of LY379268 on cell viability.
NF-kB family proteins mediate inflammatory responses and
survival signaling. Opposite to p65-p50, c-Rel containing dimers promote
transcription of anti-apoptotic genes. We determined nuclear p65-c-Rel levels by
coimmunoprecipitation. The treatment of astrocytes with LY379268 for 30 min
induced nuclear p65-c-Rel interaction (p<0.05) and it did not change
p65-c-Rel levels induced by LPS+IFN-gamma, suggesting that c-Rel-containing dimers could be
implicated in the protective role of mGluR3 in astrocytes. Our results indicate
that mGluR3 activation may exert its neuroprotective role on astrocyte
degeneration through reduction in cAMP levels, Akt activation and possibly c-Rel
activation