Perturbation of Dopamine Metabolism by 3-Amino-2-(4′-halophenyl)propenes Leads to Increased Oxidative Stress and Apoptotic SH-SY5Y Cell Death

Samms, Warren C.; Perera, Rohan P.; Wimalasena, D. Shyamali; Wimalasena, Kandatege

doi:10.1124/mol.107.035873

Cited by 5 publications

(5 citation statements)

References 40 publications

(48 reference statements)

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“…Therefore, VMAT inhibitors could be toxic to catecholaminergic neurons. In agreement with this notion, neurotoxicity of bVMAT2 inhibitors, 3-amino-2-phenylpropene (APP) derivatives in human neuroblastoma SH-SY5Y cells has been recently reported124. These derivatives are specifically toxic to SH-SY5Y, but not to non-neuronal M-1, HEPG-2 or HEK-293 cells at similar concentrations.…”

Section: Pharmacologymentioning

confidence: 64%

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Vesicular monoamine transporters: Structure‐function, pharmacology, and medicinal chemistry

Wimalasena

2011

Medicinal Research Reviews

164

140

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Vesicular monoamine transporters (VMAT) are responsible for the uptake of cytosolic monoamines into synaptic vesicles in monoaminergic neurons. Two closely related VMATs with distinct pharmacological properties and tissue distributions have been characterized. VMAT1 is preferentially expressed in neuroendocrine cells and VMAT2 is primarily expressed in the CNS. The neurotoxicity and addictive properties of various psychostimulants have been attributed, at least partly, to their interference with VMAT2 functions. The quantitative assessment of the VMAT2 density by PET scanning has been clinically useful for early diagnosis and monitoring of the progression of Parkinson's and Alzheimer's diseases and drug addiction. The classical VMAT2 inhibitor tetrabenazine has long been used for the treatment of chorea associated with Huntington's disease in UK, Canada and Australia and recently approved in the US. The VMAT2 imaging may also be useful for exploiting the onset of diabetes mellitus, since VMAT2 is also expressed in the β-cells of the pancreas. VMAT1 gene SLC18A1 is a locus with strong evidence of linkage with schizophrenia and thus, the polymorphic forms of the VMAT1 gene may confer susceptibility to schizophrenia. This review summarizes the current understanding of the structurefunction relationships of VMAT2, and the role of VMAT2 on addiction and psychostimulant induced neurotoxicity, and the therapeutic and diagnostic applications of specific VMAT2 ligands. The evidence for the linkage of VMAT1 gene with schizophrenia and bipolar disorder I are also discussed.

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Section: Pharmacologymentioning

confidence: 64%

“…DNA fragmentation analysis supports that cell death is likely due to a caspase-independent ROS-mediated apoptotic pathway. Increased oxidative stress generated by the perturbation of DA metabolism has been proposed as the cause of apoptotic SH-SY5Y cell death124.…”

Section: Pharmacologymentioning

confidence: 99%

Vesicular monoamine transporters: Structure‐function, pharmacology, and medicinal chemistry

Wimalasena

2011

Medicinal Research Reviews

164

140

View full text Add to dashboard Cite

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“…These cells have the capacity to take up, store, and metabolize dopamine. Application of dopamine to cultures of SH-SY5Y cells will result in cytotoxicity due to the generation of oxidative stress from dopamine that is not properly stored in vesicles (23). We tested whether overexpression of NQO2 can alter this dopamine-induced generation of oxidative stress.…”

Section: Resultsmentioning

confidence: 99%

Association of NRH:Quinone Oxidoreductase 2 Gene Promoter Polymorphism With Higher Gene Expression and Increased Susceptibility to Parkinson's Disease

Wang¹,

Le²,

Pan³

et al. 2008

The Journals of Gerontology Series A: Biological Sciences and M

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The N-ribosyldihydronicotinamide (NRH):quinone oxidoreductase 2 (NQO2) gene encodes an enzyme that catalyzes activation of quinones. Blood DNA from 80 control individuals and 118 age-matched Parkinson's disease patients were analyzed for NQO2 gene promoter polymorphisms. The results revealed three allelic variants, designated I-29, I-16, and D. These results were confirmed in fibroblast cell lines. In patients with Parkinson's disease, there was a significant increase in the frequency of the D allele, but there was no difference in the frequency of the alleles in familial compared to sporadic Parkinson's disease. The D and I-16 promoters direct higher NQO2 gene expression that results in higher enzyme activity. Overexpression of NQO2 in the catecholaminergic neuroblastoma SH-SY5Y cells resulted in increased production of reactive oxygen species when exposed to exogenous dopamine. The results suggest that the association of the D promoter with Parkinson's disease may be due to an increase in expression of the NQO2 gene.

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“…, it has been argued that the redistribution of DA from a smaller environment inside synaptic vesicles to oxidizing environments outside vesicles favoured the formation of ROS within the DA neurons which contribute to DA loss . Therefore, we can say that a change in DA storage and release machinery is associated with DA neurons loss, probably because of a caspase‐independent ROS‐mediated apoptotic pathway .…”

Section: Discussionmentioning

confidence: 99%

Lipid peroxidation and apoptotic response in rat brain areas induced by long‐term administration of nandrolone: the mutual crosstalk between ROS and NF‐kB

Turillazzi

Neri

Cerretani

et al. 2016

J Cellular Molecular Medi

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The aim of this study was to evaluate the played by oxidative stress in the apoptotic response in different brain areas of rats chronically treated with supra‐physiological doses of nandrolone decanoate (ND). Immunohistochemical study and Western blot analysis were performed to evaluate cells' apoptosis and to measure the effects of expression of specific mediators, such as NF‐κB (nuclear factor kappa‐light‐chain‐enhancer of activated B cells), Bcl‐2 (B‐cell lymphoma 2), SMAC/DIABLO (second mitochondria‐derived activator of caspases/direct IAP‐binding protein with low PI) and VMAT2 (vesicular monoamine transporter 2) on apoptosis. The results of the present study indicate that a long‐term administration of ND promotes oxidative injury in rat brain specific areas. A link between oxidative stress and NF‐κB signalling pathways is supported by our results. In addition to high levels of oxidative stress, we consistently observed a strong immunopositivity to NF‐κB. It has been argued that one of the pathways leading to the activation of NF‐κB could be under reactive oxygen species (ROS)‐mediated control. In fact, growing evidence suggests that although in limited doses, endogenous ROS may play an activating role in NF‐κB signalling, while above a certain threshold, they may negatively impact upon this signalling. However, a mutual crosstalk between ROS and NF‐κB exists and recent studies have shown that ROS activity is subject to negative feedback regulation by NF‐κB, and that this negative regulation of ROS is the means through which NF‐κB counters programmed cells.

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Perturbation of Dopamine Metabolism by 3-Amino-2-(4′-halophenyl)propenes Leads to Increased Oxidative Stress and Apoptotic SH-SY5Y Cell Death

Cited by 5 publications

References 40 publications

Vesicular monoamine transporters: Structure‐function, pharmacology, and medicinal chemistry

Vesicular monoamine transporters: Structure‐function, pharmacology, and medicinal chemistry

Association of NRH:Quinone Oxidoreductase 2 Gene Promoter Polymorphism With Higher Gene Expression and Increased Susceptibility to Parkinson's Disease

Lipid peroxidation and apoptotic response in rat brain areas induced by long‐term administration of nandrolone: the mutual crosstalk between ROS and NF‐kB

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