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
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.
Available from: Pimtip Sanvarinda
- "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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ABSTRACT: 6-Hydroxydopamine (6-OHDA) selectively enters dopaminergic neurons and undergoes auto-oxidation resulting in the generation of reactive oxygen species and dopamine quinones, subsequently leading to apoptosis. This mechanism mimics the pathogenesis of Parkinson's disease and has been used to induce experimental Parkinsonism in both in vitro and in vivo systems. In this study, we investigated the effects of curcumin I (diferuloylmethane) purified from Curcuma longa on quinoprotein production, phosphorylation of p38 MAPK (p-p38), and caspase-3 activation in 6-OHDA-treated SH-SY5Y dopaminergic cells. Pretreatment of SH-SY5Y with curcumin I at concentrations of 1, 5, 10, and 20 μM, significantly decreased the formation of quinoprotein and reduced the levels of p-p38 and cleaved caspase-3 in a dose-dependent manner. Moreover, the levels of the dopaminergic neuron marker, phospho-tyrosine hydroxylase (p-TH), were also dose-dependently increased upon treatment with curcumin I. Our results clearly demonstrated that curcumin I protects neurons against oxidative damage, as shown by attenuation of p-p38 expression, caspase-3-activation, and toxic quinoprotein formation, together with the restoration of p-TH levels. This study provides evidence for the therapeutic potential of curcumin I in the chemoprevention of oxidative stress-related neurodegeneration. Copyright © 2013 John Wiley & Sons, Ltd.
Phytotherapy Research 04/2014; 28(4). DOI:10.1002/ptr.5036 · 2.66 Impact Factor
Available from: ncbi.nlm.nih.gov
- "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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ABSTRACT: We have investigated whether insulin-like growth factor-1 (IGF-1) receptor signaling alters rates of apoptosis in dopamine beta-hydroxylase (Dbh(-/-)) knockout mice. Retinal lysates from Dbh(-/-) and their heterozygote littermates (Dbh(+/-)) were used to examine the role of norepinephrine in the regulation of IGF-1 receptor signaling and apoptosis in the retina. Western blot analysis was done for protein levels of total and phosphorylated IGF-1 receptor, insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), and Akt. A caspase 3 ELISA and dopamine ELISA were done on retinal lysates. To verify which regions of the retina were undergoing apoptosis, TUNEL labeling was performed. No changes in dopamine were noted between the KO and heterozygote mice. IGF-1 receptor phosphorylation was significantly decreased in Dbh(-/-) mice as compared to their heterozygote littermates (P<0.05 vs. heterozygous mice). IRS-1 protein phosphorylation was significantly decreased in KO mice (P<0.05 vs. heterozygous mice), while no significant changes were noted in IRS-2 protein phosphorylation. Akt protein phosphorylation was also reduced in the KO mice, likely leading to increased cleaved caspase 3 levels. The increase in apoptosis in the Dbh(-/-) mice occurred predominantly in the inner retina. Our results suggest that IGF-1 receptor signaling is reduced in the retina of mice with dysfunctional adrenergic receptor signaling. The data also indicate that IGF-1 receptor signaling occurs primarily through IRS-1, rather than IRS-2. The reduction in Akt phosphorylation, likely through reduced IGF-1 receptor signaling, could explain the increase in cleaved caspase 3, leading to apoptosis. These results suggest that alterations in adrenergic receptor signaling modulate IGF-1 receptor signaling, which can regulate apoptosis in the retina.
Autonomic neuroscience: basic & clinical 09/2009; 152(1-2):21-6. DOI:10.1016/j.autneu.2009.08.014 · 1.56 Impact Factor
Available from: Guillermo N Armaiz-Pena
- "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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ABSTRACT: Clinical and animal studies now support the notion that psychological factors such as stress, chronic depression, and lack of social support might promote tumor growth and progression. Recently, cellular and molecular studies have started to identify biological processes that could mediate such effects. This review provides a mechanistic understanding of the relationship between biological and behavioral influences in cancer and points to more comprehensive behavioral and pharmacological approaches for better patient outcomes.
Brain Behavior and Immunity 01/2009; 23(1):10-5. DOI:10.1016/j.bbi.2008.06.007 · 5.89 Impact Factor
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