Artículo
Melanocortin 4 receptor activation induces brain-derived neurotrophic factor expression in rat astrocytes through cyclic AMP – Protein kinase A pathway
Caruso, Carla Mariana
; Carniglia, Lila
; Durand, Daniela Elizabeth
; Gonzalez, Patricia Verónica
; Scimonelli, Teresa Nieves
; Lasaga, Mercedes Isabel
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Fecha de publicación:
01/2012
Editorial:
Elsevier Ireland
Revista:
Molecular and Cellular Endocrinology
ISSN:
0303-7207
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Melanocortin 4 receptors (MC4R) are mainly expressed in the brain. We previously showed that the anti-inflammatory action of α-melanocyte-stimulating hormone (α-MSH) in rat hypothalamus and in cultured astrocytes involved MC4R activation. However, MC4R mechanisms of action remain undetermined. Since brain-derived neurotrophic factor (BDNF) may be mediating MC4R hypothalamic anorexigenic actions, we determined melanocortin effects on BDNF expression in rat cultured astrocytes and certain mechanisms involved in MC4R signaling. α-MSH and its analogue NDP-MSH, induced production of cAMP in astrocytes. This effect was completely blocked by the MC4R antagonist, HS024. We found that NDP-MSH increased BDNF mRNA and protein levels in astrocytes. The effect of NDP-MSH on BDNF expression was abolished by the adenylate cyclase inhibitor SQ22536, and decreased by the PKA inhibitor Rp-cAMP. Since melanocortins are immunomodulators, we investigated their actions with bacterial lipopolysaccharide (LPS) and interferon-γ (IFN-γ) stimulus. Although both α-MSH and LPS + IFN-γ increased cAMP responding element binding protein (CREB) activation, LPS + IFN-γ did not modify BDNF expression. On the other hand, α-MSH did not modify basal or LPS + IFN-γ-induced nuclear factor-κB activation. Our results show for the first time that MC4R activation in astrocytes induces BDNF expression through cAMP-PKA-CREB pathway without involving NF-κB.
Palabras clave:
Melanocortins
,
Neurodegeneration
,
Neurotrophic Factors
,
Astrocytes
,
Mc4r
,
Bdnf
,
Camp
,
Pka
,
Creb
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(BIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos(IFEC)
Articulos de INST. DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Articulos de INST. DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Articulos(INBIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Citación
Caruso, Carla Mariana; Carniglia, Lila; Durand, Daniela Elizabeth; Gonzalez, Patricia Verónica; Scimonelli, Teresa Nieves; et al.; Melanocortin 4 receptor activation induces brain-derived neurotrophic factor expression in rat astrocytes through cyclic AMP – Protein kinase A pathway; Elsevier Ireland; Molecular and Cellular Endocrinology; 348; 1; 1-2012; 47-54
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