Dopaminergic and adrenergic toxicities on SK-N-MC human neuroblastoma cells are mediated through G protein signaling and oxidative stress

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.
APOPTOSIS (Impact Factor: 3.69). 02/2007; 12(1):167-79. DOI: 10.1007/s10495-006-0524-8
Source: PubMed


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 muM 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.

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    • "In conclusion, despite the pleiotropic effects of curcumin I, such as its ability to modulate key transcription factors as well as ability to promote neurogenesis (Shishodia et al., 2007), it is likely that the effects observed in this study were mediated through anti-oxidant activity. However, other mechanisms , such as G-protein-mediated signaling cascade cannot be excluded (Chan et al., 2007 "
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    Phytotherapy Research 04/2014; 28(4). DOI:10.1002/ptr.5036 · 2.66 Impact Factor
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    • "Furthermore, norepinephrine induced PC12 cell apoptosis through a mitochondrial death pathway that blocks signals from the phosphatidylinositol-3-kinase (PI3K)/Akt survival pathway (Mao et al. 2006). G-protein mediated signaling cascades can participate in the dopamine/norepinephrine-induced neuronal apoptosis in human brain (Chan et al. 2007). Therefore, much of the literature suggests that norepinephrine can induce apoptosis in a number of organs. "
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    Autonomic neuroscience: basic & clinical 09/2009; 152(1-2):21-6. DOI:10.1016/j.autneu.2009.08.014 · 1.56 Impact Factor
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    • "The continuation of the metastatic process depends on the ability of the tumor cell to survive and avoid apoptosis (Langley and Fidler, 2007). It has been shown that dopamine and norepinephrine can trigger apoptosis via a G protein-mediated signaling cascade in neuroblastoma cells, but not in lung carcinoma cells (Chan et al., 2007). More importantly, epinephrine reduced the sensitivity of prostate and breast cancer cells to apoptosis through PKA-dependent BAD phosphorylation that was mediated by β-adrenergic receptor activation (Sastry et al., 2007). "
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