Monoamine oxidase‐A modulates apoptotic cell death induced by staurosporine in human neuroblastoma cells
Open Access
- 17 August 2007
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 103 (6), 2189-2199
- https://doi.org/10.1111/j.1471-4159.2007.04921.x
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.Keywords
This publication has 39 references indexed in Scilit:
- A link between monoamine oxidase-A and apoptosis in serum deprived human SH-SY5Y neuroblastoma cellsJournal of Neural Transmission, 2007
- Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathwayProceedings of the National Academy of Sciences of the United States of America, 2006
- Type A monoamine oxidase is the target of an endogenous dopaminergic neurotoxin, N‐methyl(R)salsolinol, leading to apoptosis in SH‐SY5Y cellsJournal of Neurochemistry, 2005
- Monoamine Oxidase (MAO) in Human Peripheral TissuesNeuroToxicology, 2004
- On the Binding of Monoamine Oxidase Inhibitors to Some Sites Distinct from the MAO Active Site, and Effects Thereby ElicitedNeuroToxicology, 2004
- Dopamine Oxidation Alters Mitochondrial Respiration and Induces Permeability Transition in Brain MitochondriaJournal of Neurochemistry, 1999
- Vitamin C: poison, prophylactic or panacea?Trends in Biochemical Sciences, 1999
- Mitogen-activated protein kinase pathwaysCurrent Opinion in Cell Biology, 1997
- Activation of Mitogen-activated Protein Kinase by H2O2Published by Elsevier BV ,1996
- Brain‐Derived Neurotrophic Factor Protects Dopamine Neurons Against 6‐Hydroxydopamine and N‐Methyl‐4‐Phenylpyridinium Ion Toxicity: Involvement of the Glutathione SystemJournal of Neurochemistry, 1992