We show that treatment of cerebellar granules with interleukin-8 (IL-8), growth-related gene product beta (GRObeta) or AMPA induced activation of PI3-K/Akt and of ERK pathways, the latter being independent of PI3-K and dependent on PTX-sensitive G proteins. We also show that AMPA-mediated neuron survival was abolished both by ERK kinase inhibitor PD98059 and AMPA-Rs blocker CNQX, and that chemokine-mediated survival was blocked by the PI3-K inhibitors LY294002 and wortmannin. We conclude that the neurotrophic effects of AMPA need the contemporary activation of ERKs and stimulation of AMPA-Rs, and that PI3-K/Akt activation is a determinant pathway for the lL-8/GRObeta anti-apoptotic activity.
Signaling pathways acticated by chemokine receptor CXCR2 and AMPA-type glutamate receptors and involvement in granule cells survival / Limatola, Cristina; Ciotti, Mt; Mercanti, D; Santoni, Angela; Eusebi, Fabrizio. - In: JOURNAL OF NEUROIMMUNOLOGY. - ISSN 0165-5728. - STAMPA. - 123:(2002), pp. 9-17. [10.1016/S0165-5728(01)00472-6]
Signaling pathways acticated by chemokine receptor CXCR2 and AMPA-type glutamate receptors and involvement in granule cells survival
LIMATOLA, Cristina;SANTONI, Angela;EUSEBI, Fabrizio
2002
Abstract
We show that treatment of cerebellar granules with interleukin-8 (IL-8), growth-related gene product beta (GRObeta) or AMPA induced activation of PI3-K/Akt and of ERK pathways, the latter being independent of PI3-K and dependent on PTX-sensitive G proteins. We also show that AMPA-mediated neuron survival was abolished both by ERK kinase inhibitor PD98059 and AMPA-Rs blocker CNQX, and that chemokine-mediated survival was blocked by the PI3-K inhibitors LY294002 and wortmannin. We conclude that the neurotrophic effects of AMPA need the contemporary activation of ERKs and stimulation of AMPA-Rs, and that PI3-K/Akt activation is a determinant pathway for the lL-8/GRObeta anti-apoptotic activity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.