Vasoinhibin Suppresses Nerve Growth Factor-Induced Differentiation and Survival of PC12 Pheochromocytoma Cells
Por:
Melo, Zesergio, Castillo, Ximena, Moreno-Carranza, Bibiana, Ledesma-Colunga, Maria G., Arnold, Edith, Lopez-Casillas, Fernando, Ruiz-Herrera, Xarubet, Clapp, Carmen, Martinez de la Escalera, Gonzalo
Publicada:
1 ene 2019
Resumen:
Background: Vasoinhibin, a protein derived from prolactin, regulates various vascular functions including endothelial cell survival. Of note, vasoinhibin is present in the central nervous system, where it triggers neuroendocrine and behavioral responses to stress. Moreover, vasoinhibin compromises nerve growth factor (NGF)-induced neurite outgrowth in primary sensory neurons of the peripheral nervous system. Nonetheless, information on the functions of vasoinhibin in developing neurons remains limited. The present study explored whether vasoinhibin affects the neurotrophic actions of NGF by measuring the cell differentiation and survival of PC12 pheochromocytoma cells. Methods: The effects of recombinant or lentiviral vector-transduced human vasoinhibin were tested on differentiating PC12 cells. Neurite outgrowth was quantified by measuring their length and density. The MTT assay was employed to assess cell viability, and ELISA was used to quantify DNA fragmentation as an index of apoptosis. Phosphorylated Akt and ERK1/2 were analyzed by Western blotting. Results: The addition of a human recombinant vasoinhibin, and the transduction of a lentiviral vector carrying a human vasoinhibin sequence, significantly reduced NGF-induced neurite outgrowth, cell survival, and phosphorylation of Akt and ERK1/2, and increased DNA fragmentation and caspase 3 activation in PC12 cells. Conclusions: Vasoinhibin downregulates NGF-induced differentiation and survival of PC12 cells, blocking tropomyosin receptor kinase A-triggered signaling pathways and increasing apoptosis. These results establish that vasoinhibin interaction with NGF and other neurotrophins may be critical in mediating pathways involved in neuronal survival and differentiation. © 2019 S. Karger AG, Basel. All rights reserved.
Filiaciones:
Melo, Zesergio:
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Blvd. Juriquilla 3001, Querétaro, 76230, Mexico
UNAM, Inst Neurobiol, Campus UNAM Juriquilla,Blvd Juriquilla 3001, Queretaro 76230, Mexico
Castillo, Ximena:
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Blvd. Juriquilla 3001, Querétaro, 76230, Mexico
UNAM, Inst Neurobiol, Campus UNAM Juriquilla,Blvd Juriquilla 3001, Queretaro 76230, Mexico
Moreno-Carranza, Bibiana:
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Blvd. Juriquilla 3001, Querétaro, 76230, Mexico
UNAM, Inst Neurobiol, Campus UNAM Juriquilla,Blvd Juriquilla 3001, Queretaro 76230, Mexico
Ledesma-Colunga, Maria G.:
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Blvd. Juriquilla 3001, Querétaro, 76230, Mexico
UNAM, Inst Neurobiol, Campus UNAM Juriquilla,Blvd Juriquilla 3001, Queretaro 76230, Mexico
Arnold, Edith:
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Blvd. Juriquilla 3001, Querétaro, 76230, Mexico
Catedrática CONACYT, Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro, Mexico
UNAM, Inst Neurobiol, Campus UNAM Juriquilla,Blvd Juriquilla 3001, Queretaro 76230, Mexico
UNAM, Inst Neurobiol, Campus UNAM Juriquilla, Queretaro, Mexico
Lopez-Casillas, Fernando:
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Ciudad Univ, Mexico City, DF, Mexico
Ruiz-Herrera, Xarubet:
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Blvd. Juriquilla 3001, Querétaro, 76230, Mexico
UNAM, Inst Neurobiol, Campus UNAM Juriquilla,Blvd Juriquilla 3001, Queretaro 76230, Mexico
Clapp, Carmen:
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Blvd. Juriquilla 3001, Querétaro, 76230, Mexico
UNAM, Inst Neurobiol, Campus UNAM Juriquilla,Blvd Juriquilla 3001, Queretaro 76230, Mexico
Martinez de la Escalera, Gonzalo:
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Blvd. Juriquilla 3001, Querétaro, 76230, Mexico
UNAM, Inst Neurobiol, Campus UNAM Juriquilla,Blvd Juriquilla 3001, Queretaro 76230, Mexico
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