IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
MAPK/JNK pathways and the molecular chaperone Hsp90 are involved in immunophilin-dependent neurodifferentiation
Autor/es:
PATIÑO M, DANERI C, GALIGNIANA MD
Reunión:
Congreso; LXII Reunión Anual de SAIC; 2017
Institución organizadora:
SAIC
Resumen:
In nervous cells, cellular differentiation occurs through various eliciting agents such as retinoic acid. Our laboratory has previously demonstrated that the immunophilin-ligand FK506 is a good neurotrophic factor. In this study, it was evaluated the possible signaling cascade involved in such process. N2a mouse neuroblastoma cells were stimulated with 1 µM FK506 or 1 µM retinoic acid (for comparative purposes). Using neurite length as a differentiation parameter, FK506 showed as a stronger neurodifferentiation inducer. Then, cells were treated with different inhibitors. It was found that after inhibiting ERK1/2 activation (MAPK pathway) with the MAPK1 inhibitor PD98059, cells showed shorter neurites, suggesting that this pathway is involved in FK506 action. JNK pathway was also involved since the inhibitor SP600125 exhibited similar inhibitory action as the MAPK1 inhibitor. Nonetheless, SP600125 also showed an increasing number of neurites per cell. In previous works of our laboratory, where the role of molecular chaperones was analyzed, it was suggested the involvement of Hsp90 ATPase activity in neuronal differentiation, whereas other work in the literature reported inhibitory action. Due to this discrepancy, the requirement of Hsp90 biological activity for the neurodifferentiation process was tested using radicicol, a known Hsp90 inhibitor of its ATPase activity. Cells showed even longer neurites than those treated with FK506, and also showed more varicosities (usually seen in mature neurons). Taking together, these observations suggest that the MAPK and JNK pathways mediate FK506-dependent differentiation, and that the inhibition of Hsp90 activity is also a positive regulatory mechanism.