Dopaminergic and adrenergic toxicities on SK-N-MC human neuroblastoma cells are mediated through G protein signaling and oxidative stress |
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Authors: | Anthony S L Chan Linda W C Ng Lydia S W Poon Winnie W Y Chan Yung H Wong |
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Institution: | (1) Department of Biochemistry, the Molecular Neuroscience Center, and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China |
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Abstract: | Dopamine and norepinephrine are neurotransmitters which participate in various regulatory functions of the human brain. These
functions are lost in neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease. In this study, we
used SK-N-MC neuroblastoma cells to investigate the cytotoxicities of high concentrations of dopamine and norepinephrine on
neuronal cells. Dopamine, norepinephrine, as well as their corresponding synthetic agonists (SKF38393 and isoproterenol, respectively)
triggered SK-N-MC cell death when applied at 50–100 μM persistently for 2 days. This catecholamine-induced cell death appears
to be neuronal specific, as demonstrated by their inabilities of triggering apoptosis of A549 lung carcinoma cells and Cos-7
kidney fibroblasts. By pretreating SK-N-MC cells with target-specific inhibitors before administration of catecholamine, components
of G protein signaling (i.e. G
s
/cAMP/PKA), monoamine oxidases, nitric oxide synthase, c-Jun N-terminal kinase and oxidative stress were found to be involved in this dopamine/norepinephrine-induced cytotoxicity,
which subsequently led to caspase-dependent and -independent apoptotic responses as well as DNA degradation. In contrast,
agonists of G
i
-coupled dopamine receptors and adrenergic receptors (quinpirole and UK14,304, respectively) were incapable of triggering
apoptosis of SK-N-MC cells. Our results suggest that both G protein (G
s
)-mediated signaling cascade and oxidative stress participate in the dopamine/norepinephrine-induced neuronal apoptosis.
Anthony Chan and Ng Contributed equally to this work. |
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Keywords: | Apoptosis Dopamine G protein Neurodegeneration Norepinephrine Oxidative stress |
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