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dc.contributor.authorCarleton, Laura A.
dc.contributor.authorDoyle, Karen M.
dc.contributor.authorSamali, Afshin
dc.contributor.authorGorman, Adrienne
dc.contributor.authorMnich, Katarzyna
dc.contributor.authorKavanagh, Edel T.
dc.date.accessioned2016-01-21T12:35:21Z
dc.date.available2016-01-21T12:35:21Z
dc.date.issued2014-05-01
dc.identifier.citationMnich, K,Carleton, LA,Kavanagh, ET,Doyle, KM,Samali, A,Gorman, AM (2014) 'Nerve growth factor-mediated inhibition of apoptosis post-caspase activation is due to removal of active caspase-3 in a lysosome-dependent manner'. Cell Death & Disease, 5 .en_IE
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/10379/5469
dc.description.abstractNerve 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.en_IE
dc.description.sponsorshipScience Foundation Ireland (Grant No. 09/RFP/BMT2153), Irish Research Council for Science, Engineering and Technology (EMBARK scholarships), Breast Cancer campaign, UK (Grant number 2008NovPhD21), Thomas Crawford Hayes fund, School of Natural Sciences, NUI Galway, Ireland, Beckman fund, School of Natural Sciences, NUI Galway, Irelanden_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherNature Publishing Groupen_IE
dc.relation.ispartofCell Death & Diseaseen
dc.subjectApoptosisen_IE
dc.subjectAutophagyen_IE
dc.subjectCaspasesen_IE
dc.subjectLysosomesen_IE
dc.subjectNerve growth factor (NGF)en_IE
dc.subjectCytochrome-c releaseen_IE
dc.subjectProgrammed cell-deathen_IE
dc.subjectSympathetic neuronsen_IE
dc.subjectPhosphatidylserine exposureen_IE
dc.subjectPheochromocytoma cellsen_IE
dc.subjectTyrosine kinaseen_IE
dc.subjectLigase activityen_IE
dc.subjectMitochondriaen_IE
dc.subjectDegradationen_IE
dc.subjectAutophagyen_IE
dc.subjectBiochemistryen_IE
dc.titleNerve growth factor-mediated inhibition of apoptosis post-caspase activation is due to removal of active caspase-3 in a lysosome-dependent manneren_IE
dc.typeArticleen_IE
dc.date.updated2016-01-21T11:57:57Z
dc.identifier.doi10.1038/cddis.2014.173
dc.local.publishedsourcehttp://dx.doi.org/doi:10.1038/cddis.2014.173en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funder|~|
dc.internal.rssid6679296
dc.local.contactAdrienne Gorman, Biochemistry, School Of Natural Science, Bioresearch Building, Nui. 2417 Email: adrienne.gorman@nuigalway.ie
dc.local.copyrightcheckedNo
dc.local.versionACCEPTED
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