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Monoamine oxidase-A modulates apoptotic cell death induced by staurosporine in human neuroblastoma cells.
J Neurochem. 2007 Dec; 103(6):2189-99.JN

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.

Authors+Show Affiliations

School of Biomedical and Natural Sciences, Nottingham Trent University, Clifton, Nottingham, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17883400

Citation

Fitzgerald, Julia C., et al. "Monoamine oxidase-A Modulates Apoptotic Cell Death Induced By Staurosporine in Human Neuroblastoma Cells." Journal of Neurochemistry, vol. 103, no. 6, 2007, pp. 2189-99.
Fitzgerald JC, Ufer C, De Girolamo LA, et al. Monoamine oxidase-A modulates apoptotic cell death induced by staurosporine in human neuroblastoma cells. J Neurochem. 2007;103(6):2189-99.
Fitzgerald, J. C., Ufer, C., De Girolamo, L. A., Kuhn, H., & Billett, E. E. (2007). Monoamine oxidase-A modulates apoptotic cell death induced by staurosporine in human neuroblastoma cells. Journal of Neurochemistry, 103(6), 2189-99.
Fitzgerald JC, et al. Monoamine oxidase-A Modulates Apoptotic Cell Death Induced By Staurosporine in Human Neuroblastoma Cells. J Neurochem. 2007;103(6):2189-99. PubMed PMID: 17883400.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Monoamine oxidase-A modulates apoptotic cell death induced by staurosporine in human neuroblastoma cells. AU - Fitzgerald,Julia C, AU - Ufer,Christoph, AU - De Girolamo,Luigi A, AU - Kuhn,Hartmut, AU - Billett,E Ellen, Y1 - 2007/09/18/ PY - 2007/9/22/pubmed PY - 2008/1/9/medline PY - 2007/9/22/entrez SP - 2189 EP - 99 JF - Journal of neurochemistry JO - J Neurochem VL - 103 IS - 6 N2 - 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. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/17883400/Monoamine_oxidase_A_modulates_apoptotic_cell_death_induced_by_staurosporine_in_human_neuroblastoma_cells_ L2 - https://doi.org/10.1111/j.1471-4159.2007.04921.x DB - PRIME DP - Unbound Medicine ER -