ArticleBiochimica et biophysica acta2012
Overexpression of VMAT-2 and DT-diaphorase protects substantia nigra-derived cells against aminochrome neurotoxicity.
Article in Biochimica et biophysica acta, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- The Enigma of Neuromelanin: How Animal Models Can Help Researchers to Understand the Link Between Pigments and Neurodegeneration.Biomedicines · 2025Review
- LRRK2-mediated mitochondrial dysfunction in Parkinson's disease.The Biochemical journal · 2025Review
- G2019S selective LRRK2 kinase inhibitor abrogates mitochondrial DNA damage.NPJ Parkinson's disease · 2024Article
- A blood-based marker of mitochondrial DNA damage in Parkinson's disease.Science translational medicine · 2023Article
- The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know.International journal of molecular sciences · 2021Review
- Cellular Trafficking of Glutathione Transferase M2-2 Between U373MG and SHSY-S7 Cells is Mediated by Exosomes.Neurotoxicity research · 2021Article
- The "Sick-but-not-Dead" Phenomenon Applied to Catecholamine Deficiency in Neurodegenerative Diseases.Seminars in neurology · 2020Review
- How Important Is the Use of Cocaine and Amphetamines in the Development of Parkinson Disease? A Computational Study.Neurotoxicity research · 2020Article
- The catecholaldehyde hypothesis: where MAO fits in.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- Novel Alpha-Synuclein Oligomers Formed with the Aminochrome-Glutathione Conjugate Are Not Neurotoxic.Neurotoxicity research · 2019Article
- DT-Diaphorase Prevents Aminochrome-Induced Lysosome Dysfunction in SH-SY5Y Cells.Neurotoxicity research · 2019Article
- On the Role of Aminochrome in Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Parkinson's Disease.Frontiers in neuroscience · 2019Article
- Overexpression of Vesicular Monoamine Transporter-2 may Block Neurotoxic Metabolites from Cytosolic Dopamine: a Potential Neuroprotective Therapy for Parkinson's Disease.Clinical pharmacology and translational medicine · 2019Article
- Neurotoxins as Preclinical Models for Parkinson's Disease.Neurotoxicity research · 2018Review
- DT-diaphorase Protects Against Autophagy Induced by Aminochrome-Dependent Alpha-Synuclein Oligomers.Neurotoxicity research · 2017Article
- Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease.Progress in neurobiology · 2017Review
- On the Role of DT-Diaphorase Inhibition in Aminochrome-Induced Neurotoxicity In Vivo.Neurotoxicity research · 2017Article
- On the role of endogenous neurotoxins and neuroprotection in Parkinson's disease.Neural regeneration research · 2017Review
- Aminochrome induces dopaminergic neuronal dysfunction: a new animal model for Parkinson's disease.Cellular and molecular life sciences : CMLS · 2016Article
- Commentary: A Humanized Clinically Calibrated Quantitative Systems Pharmacology Model for Hypokinetic Motor Symptoms in Parkinson's Disease.Frontiers in pharmacology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
We tested the hypothesis that both VMAT-2 and DT-diaphorase are an important cellular defense against aminochrome-dependent neurotoxicity during dopamine oxidation. A cell line with VMAT-2 and DT-diaphorase over-expressed was created. The transfection of RCSN-3 cells with a bicistronic plasmid coding for VMAT-2 fused with GFP-IRES-DT-diaphorase cDNA induced a significant increase in protein expression of VMAT-2 (7-fold; P<0.001) and DT-diaphorase (9-fold; P<0.001), accompanied by a 4- and 5.5-fold significant increase in transport and enzyme activity, respectively. Studies with synaptic vesicles from rat substantia nigra revealed that VMAT-2 uptake of ³H-aminochrome 6.3 ± 0.4nmol/min/mg was similar to dopamine uptake 6.2 ± 0.3nmol/min/mg that which were dependent on ATP. Interestingly, aminochrome uptake was inhibited by 2μM lobeline but not reserpine (1 and 10μM). Incubation of cells overexpressing VMAT-2 and DT-diaphorase with 20μM aminochrome resulted in (i) a significant decrease in cell death (6-fold, P<0.001); (ii) normal ultra structure determined by transmission electron microscopy contrasting with a significant increase of autophagosome and a dramatic remodeling of the mitochondrial inner membrane in wild type cells; (iii) normal level of ATP (256 ± 11μM) contrasting with a significant decrease in wild type cells (121±11μM, P<0.001); and (iv) a significant decrease in DNA laddering (21 ± 8pixels, P<0.001) cells in comparison with wild type cells treated with 20μM aminochrome (269 ± 9). These results support our hypothesis that VMAT-2 and DT-diaphorase are an important defense system against aminochrome formed during dopamine oxidation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.