Survival of motor neuron protein over-expression prevents calpain-mediated cleavage and activation of procaspase-3 in differentiated human SH-SY5Y cells

R.S. Anderton; B.P. Meloni; F.L. Mastaglia; W.K. Greene; S. Boulos

doi:10.1016/j.neuroscience.2011.02.032

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Survival of motor neuron protein over-expression prevents calpain-mediated cleavage and activation of procaspase-3 in differentiated human SH-SY5Y cells

Journal article

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Survival of motor neuron protein over-expression prevents calpain-mediated cleavage and activation of procaspase-3 in differentiated human SH-SY5Y cells

R.S. Anderton, B.P. Meloni, F.L. Mastaglia, W.K. Greene and S. Boulos

Neuroscience, Vol.181, pp.226-233

2011

DOI: https://doi.org/10.1016/j.neuroscience.2011.02.032

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Abstract

Spinal muscular atrophy (SMA), a neurodegenerative disorder primarily affecting motor neurons, is the most common genetic cause of infant death. This incurable disease is caused by the absence of a functional SMN1 gene and a reduction in full length survival of motor neuron (SMN) protein. In this study, a neuroprotective function of SMN was investigated in differentiated human SH-SY5Y cells using an adenoviral vector to over-express SMN protein. The pro-survival capacity of SMN was assessed in an Akt/PI3-kinase inhibition (LY294002) model, as well as an oxidative stress (hydrogen peroxide) and excitotoxic (glutamate) model. SMN over-expression in SH-SY5Y cells protected against Akt/phosphatidylinositol 3-kinase (PI3-kinase) inhibition, but not oxidative stress, nor against excitotoxicity in rat cortical neurons. Western analysis of cell homogenates from SH-SY5Y cultures over-expressing SMN harvested pre- and post-Akt/PI3-kinase inhibition indicated that SMN protein inhibited caspase-3 activation via blockade of calpain-mediated procaspase-3 cleavage. This study has revealed a novel anti-apoptotic function for the SMN protein in differentiated SH-SY5Y cells. Finally, the cell death model described herein will allow the assessment of future therapeutic agents or strategies aimed at increasing SMN protein levels.

Details

Title: Survival of motor neuron protein over-expression prevents calpain-mediated cleavage and activation of procaspase-3 in differentiated human SH-SY5Y cells
Authors/Creators: R.S. Anderton (Author/Creator) - The University of Western Australia
B.P. Meloni (Author/Creator) - Centre for Neuromuscular and Neurological Disorders
F.L. Mastaglia (Author/Creator) - The University of Western Australia
W.K. Greene (Author/Creator) - Murdoch University
S. Boulos (Author/Creator) - The University of Western Australia
Publication Details: Neuroscience, Vol.181, pp.226-233
Publisher: Elsevier BV
Identifiers: 991005546040907891
Copyright: 2011 IBRO
Murdoch Affiliation: School of Veterinary and Biomedical Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.255 Musculoskeletal Disorders; 1.255.2204 Spinal Muscular Atrophy
Web Of Science research areas: Neurosciences
ESI research areas: Neuroscience & Behavior