Affordable Access

deepdyve-link
Publisher Website

Nerve growth factor-mediated inhibition of apoptosis post-caspase activation is due to removal of active caspase-3 in a lysosome-dependent manner.

Authors
  • Mnich, K1
  • Carleton, L A2
  • Kavanagh, E T2
  • Doyle, K M3
  • Samali, A2
  • Gorman, A M2
  • 1 1] Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Galway, Ireland [2] Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland. , (Ireland)
  • 2 Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Galway, Ireland. , (Ireland)
  • 3 School of Medicine, National University of Ireland, Galway, Ireland. , (Ireland)
Type
Published Article
Journal
Cell Death and Disease
Publisher
Springer Nature
Publication Date
May 01, 2014
Volume
5
Identifiers
DOI: 10.1038/cddis.2014.173
PMID: 24787014
Source
Medline
Language
English
License
Unknown

Abstract

Nerve growth factor (NGF) is well characterised as an important pro-survival factor in neuronal cells that can inhibit apoptotic cell death upstream of mitochondrial outer membrane permeabilisation. Here we addressed the question of whether NGF can also protect against apoptosis downstream of caspase activation. NGF treatment promoted a rapid reduction in the level of the p17 subunit of active caspase-3 in PC12 cells that had been induced to undergo apoptosis by various cytotoxins. The mechanism involved TrkA-dependent activation of extracellular signal-regulated kinase (ERK1/2) but not phosphatidylinositol 3-kinase (PI3K)/Akt, and de novo protein synthesis. Involvement of inhibitor of apoptosis proteins (IAPs) and proteasomal degradation were ruled out. In contrast, inhibition of lysosome function using chloroquine and concanamycin A reversed NGF-induced removal of p17. Moreover, in NGF-treated cells, active caspases were found to be localised to lysosomes. The involvement of macroautophagy and chaperone-mediated autophagy were ruled out. Taken together, these findings suggest an anti-apoptotic mechanism by which NGF induces removal of active caspase-3 in a lysosome-dependent manner.

Report this publication

Statistics

Seen <100 times