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dc.contributor.authorSoo, KY
dc.contributor.authorAtkin, JD
dc.contributor.authorFarg, M
dc.contributor.authorWalker, AK
dc.contributor.authorHorne, MK
dc.contributor.authorNagley, P
dc.date.available2017-08-08T00:17:57Z
dc.date.available2012-03-15
dc.date.available2012-03-15
dc.date.available2012-03-15
dc.date.issued2012-04-16
dc.identifierpii: PONE-D-11-23258
dc.identifier.citationSoo, K. Y., Atkin, J. D., Farg, M., Walker, A. K., Horne, M. K. & Nagley, P. (2012). Bim Links ER Stress and Apoptosis in Cells Expressing Mutant SOD1 Associated with Amyotrophic Lateral Sclerosis. PLOS ONE, 7 (4), https://doi.org/10.1371/journal.pone.0035413.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/191453
dc.description.abstractEndoplasmic reticulum (ER) stress is an important pathway to cell death in amyotrophic lateral sclerosis (ALS). We previously demonstrated that ER stress is linked to neurotoxicity associated with formation of inclusions of mutant Cu,Zn-superoxide dismutase 1 (SOD1). Cells bearing mutant inclusions undergo mitochondrial apoptotic signalling. Here, we demonstrate that the BH3-only protein, Bim, is a direct link between ER stress and mitochondrial apoptosis. In the murine neuroblastoma cell line, Neuro2a, bearing mutant SOD1 inclusions, indicators of both ER stress and apoptosis are expressed. Bim knockdown by siRNA significantly reduced nuclear apoptotic features in these inclusion-bearing cells (but did not affect the proportion of cells overall that bear inclusions). Further, both Bax recruitment to mitochondria and cytochrome c redistribution were also decreased under Bim-depletion conditions. However, upregulation of CHOP, a marker of ER stress, was not reduced by Bim knockdown. Significantly, knockdown of CHOP by siRNA reduced the extent of apoptosis in cells bearing mutant SOD1 inclusions. These sequential links between ER stress, CHOP upregulation, and Bim activation of mitochondrial apoptotic signalling indicate a clear pathway to cell death mediated by mutant SOD1.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.titleBim Links ER Stress and Apoptosis in Cells Expressing Mutant SOD1 Associated with Amyotrophic Lateral Sclerosis
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0035413
melbourne.affiliation.departmentFlorey Department of Neuroscience and Mental Health
melbourne.affiliation.departmentCentre for Neuroscience
melbourne.source.titlePLOS ONE
melbourne.source.volume7
melbourne.source.issue4
melbourne.identifier.nhmrc236805
melbourne.identifier.nhmrc400058
melbourne.identifier.nhmrc454749
dc.rights.licenseCC BY
melbourne.elementsid347632
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327676
melbourne.contributor.authorATKIN, JULIE
melbourne.contributor.authorHorne, Malcolm
melbourne.contributor.authorWALKER, ADAM
dc.identifier.eissn1932-6203
melbourne.identifier.fundernameidDEPARTMENT OF HEALTH, 236805
melbourne.identifier.fundernameidNHMRC, 236805
melbourne.identifier.fundernameidNHMRC, 400058
melbourne.identifier.fundernameidNHMRC, 454749
pubs.acceptance.date2012-03-15
melbourne.accessrightsOpen Access


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