Vasoinhibin Suppresses Nerve Growth Factor-Induced Differentiation and Survival of PC12 Pheochromocytoma Cells

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Zesergio Melo - , Universidad Nacional Autónoma de México (Author)
  • Ximena Castillo - , Universidad Nacional Autónoma de México (Author)
  • Bibiana Moreno-Carranza - , Universidad Nacional Autónoma de México (Author)
  • María G. Ledesma-Colunga - , Universidad Nacional Autónoma de México (Author)
  • Edith Arnold - , Universidad Nacional Autónoma de México (Author)
  • Fernando López-Casillas - , Universidad Nacional Autónoma de México (Author)
  • Xarubet Ruíz-Herrera - , Universidad Nacional Autónoma de México (Author)
  • Carmen Clapp - , Universidad Nacional Autónoma de México (Author)
  • Gonzalo Martínez De La Escalera - , Universidad Nacional Autónoma de México (Author)

Abstract

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 NGFinduced 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.

Details

Original languageEnglish
Pages (from-to)152-164
Number of pages13
JournalNeuroendocrinology
Volume109
Issue number2
Publication statusPublished - 1 Aug 2019
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 31091528
ORCID /0000-0002-2061-8663/work/150329809