Pathways of survival induced by NGF and extracellular ATP after growth factor deprivation

Nadia D'Ambrosi, Barbara Murra, Fabrizio Vacca, Cinzia Volonté

Research output: Contribution to journalArticle

Abstract

In a previous work we demonstrated that extracellular adenosine-5′ -triphosphate (ATP), acting on P2 receptors, exerts neuritogenic and trophic effects on the phaeochromocytoma PC12 cell line. These actions are comparable to those sustained by nerve growth factor (NGF) and involve several overlapping pathways. In this work, we describe some of the mechanisms recruited by ATP and NGF in maintaining PC12 cell survival after serum deprivation. We show that both ATP and NGF upregulate the expression of the stress-induced heat shock protein HSP70 and HSP90, whilst glucose-response protein GRP75 and GRP78 are not affected. In parallel with NGF, ATP prevents the cleavage and activation of caspase-2 and inhibits the release of cytochrome c from mitochondria into the cytoplasm. Finally, neither NGF, nor ATP directly modulate the expression of P2 receptors in the induction of cell survival. Our data contribute to dissect the biological mechanisms activated by extracellular purines exerting trophic actions and to establish that survival and neurite outgrowth lie on different mechanistic pathways.

Original languageEnglish
Pages (from-to)93-100
Number of pages8
JournalProgress in Brain Research
Volume146
DOIs
Publication statusPublished - 2004

Keywords

  • Caspase-2
  • Cytochrome c
  • Heat shock proteins
  • P2 receptor
  • PC12 cells

ASJC Scopus subject areas

  • Neuroscience(all)

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