SCIMONELLI TERESA NIEVES
Congresos y reuniones científicas
Título:
Activation of MC4R modulates cAMP, CREB and BDNF levels in rat astrocytes
Autor/es:
C. CARUSO; D. DURAND; L. CARNIGLIA; P.GONZALEZ; T SCIMONELLI; MI LASAGA
Lugar:
San Diego
Reunión:
Congreso; 40th Annual Meeting Society for Neuroscience (SFN); 2010
Institución organizadora:
Society for Neuroscience
Resumen:
Abstract: Melanocortins are neuropeptides with anti-inflammatory properties. Melanocortin 4 receptor (MC4R) is the only MCR expressed in astrocytes and our previous results demonstrated that MC4R activation mediates anti-inflammatory action of melanocortins in these cells. Since anti-inflammatory effects could have therapeutical benefits, we decided to study the mechanisms involved in MC4R activation in cultured rat astrocytes. Since MCRs are G protein-coupled receptors we determine the intracellular levels of cAMP in astrocytes after 20 min of stimulation. In a dose response curve we found that alpha-MSH 1 uM elicited the highest increase in intracellular cAMP levels. This effect was blocked by HS024, a MC4R selective antagonist which per se decreased cAMP production. On the other hand, the inflammatory stimulus LPS+IFN-gamma decreased cAMP production but the presence of alpha-MSH reverted this effect. However, both alpha-MSH and LPS+IFN-gamma treatments induced the activation of CREB measured by EMSA in proteins from nuclear extracts after 1 h incubation. On the other hand, alpha-MSH had no effect on the activation of nuclear factor-kB induced by LPS+IFN-gamma measured by Western blot. Furthermore, the analogue NDP-MSH increased brain-derived neurotrophic factor (BDNF) protein levels after 24 h, suggesting that this neurotrophic factor could be a mediator of MC4R effects. In summary, activation of MC4R leads to an increase in cAMP levels, CREB activation and BDNF expression in rat astrocytes reinforcing the central anti-inflammatory role of alpha-MSH.
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