Bim Links ER Stress and Apoptosis in Cells Expressing Mutant SOD1 Associated with Amyotrophic Lateral Sclerosis
Kai Y Soo, Julie D Atkin, Manal Farg, Adam K Walker, Malcolm K Horne, Phillip Nagley
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2012
Endoplasmic 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 ce..View full abstract
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Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by NHMRC
Funding was obtained from grants from the National Health and Medical Research Council of Australia (NHMRC), www.nhmrc.gov.au, Program Grant on Brain Injury and Repair (236805) to M. Horne and P. Nagley, and Project Grant (454749) to J. Atkin; Bethlehem Griffiths Research Foundation, www.bethlehemgrf.com.au, to J. Atkin and M. Horne; and Motor Neurone Disease Research Institute of Australia, www.mndaust.asn.au/mndria, to J. Atkin. M. Horne was supported by an NHMRC Practitioner Fellowship (400058). J. Atkin was supported by a Fellowship from the Motor Neurone Disease Research Institute of Australia. A. Walker was supported by an Australian Postgraduate Award administered through the University of Melbourne, http://cms.services.unimelb.edu.au/scholarships/pgrad/local/available/apa, and a scholarship from the Australian Rotary Health Research Fund, www.australianrotaryhealth.org.au. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.