Monoamine oxidase-A modulates apoptotic cell death induced by staurosporine in human neuroblastoma cells

FITZGERALD, J.C., UFER, C., DE GIROLAMO, L.A., KUHN, H. and BILLETT, E.E., 2007. Monoamine oxidase-A modulates apoptotic cell death induced by staurosporine in human neuroblastoma cells. Journal of Neurochemistry, 103 (6), pp. 2189-2199. ISSN 0022-3042

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Abstract

Monoamine oxidases (MAOs) are mitochondrial enzymes which control the levels of neurotransmitters in the brain and dietary amines in peripheral tissues via oxidative deamination. MAO has also been implicated in cell signalling. In this study, we describe the MAO-A isoform as functional in apoptosis induced by staurosporine (STS) in human dopaminergic neuroblastoma cells (SH-SY5Y). Increased levels of MAO-A activity were induced by STS, accompanied by increased MAO-A protein and activation of the initiator of the intrinsic pathway, caspase 9, and the executioner caspase 3. MAO-A mRNA levels were unaffected by STS, suggesting that changes in MAO-A protein are due to post-transcriptional events. Two unrelated MAO-A inhibitors reduced caspase activation. STS treatment resulted in sustained activation of the mitogen-activated protein kinase pathway enzymes extracellular regulated kinase, c-jun terminal kinase and p38, and depletion of the anti-apoptotic protein Bcl-2. These changes were significantly reversed by MAO inhibition. Production of reactive oxygen species was increased following STS exposure, which was blocked by both MAO inhibition and the antioxidant N-acetylcysteine. Therefore our data provide evidence that MAO-A, through its production of reactive oxygen species as a by-product of its catalytic activity on the mitochondrial surface, is recruited by the cell to enhance apoptotic signalling.

Item Type: Journal article
Description: The definitive version is available at www3.interscience.wiley.com
Publication Title: Journal of Neurochemistry
Creators: Fitzgerald, J.C., Ufer, C., De Girolamo, L.A., Kuhn, H. and Billett, E.E.
Publisher: Wiley-Blackwell
Date: 2007
Volume: 103
Number: 6
ISSN: 0022-3042
Identifiers:
NumberType
10.1111/j.1471-4159.2007.04921.xDOI
Rights: © 2007 International Society for Neurochemistry
Divisions: Schools > School of Science and Technology
Depositing User: EPrints Services
Date Added: 09 Oct 2015 09:42
Last Modified: 09 Jun 2017 13:08
URI: http://irep.ntu.ac.uk/id/eprint/1309

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