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• W2107720385 abstract "Aminochrome, the precursor of neuromelanin, has been proposed to be involved in the neurodegeneration neuromelanin-containing dopaminergic neurons in Parkinson’s disease. We aimed to study the mechanism of aminochrome-dependent cell death in a cell line derived from rat substantia nigra. We found that aminochrome (50μM), in the presence of NAD(P)H-quinone oxidoreductase, EC 1.6.99.2 (DT)-diaphorase inhibitor dicoumarol (DIC) (100μM), induces significant cell death (62 ± 3%; p < 0.01), increase in caspase-3 activation (p < 0.001), release of cytochrome C, disruption of mitochondrial membrane potential (p < 0.01), damage of mitochondrial DNA, damage of mitochondria determined with transmission electron microscopy, a dramatic morphological change characterized as cell shrinkage, and significant increase in number of autophagic vacuoles. To determine the role of autophagy on aminochrome-induced cell death, we incubated the cells in the presence of vinblastine and rapamycin. Interestingly, 10μM vinblastine induces a 5.9-fold (p < 0.001) and twofold (p < 0.01) significant increase in cell death when the cells were incubated with 30μM aminochrome in the absence and presence of DIC, respectively, whereas 10μM rapamycin preincubated 24 h before addition of 50μM aminochrome in the absence and the presence of 100μM DIC induces a significant decrease (p < 0.001) in cell death. In conclusion, autophagy seems to be an important protective mechanism against two different aminochrome-induced cell deaths that initially showed apoptotic features. The cell death induced by aminochrome when DT-diaphorase is inhibited requires activation of mitochondrial pathway, whereas the cell death induced by aminochrome alone requires inhibition of autophagy-dependent degrading of damaged organelles and recycling through lysosomes." @default.
• W2107720385 created "2016-06-24" @default.
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• W2107720385 date "2011-03-21" @default.
• W2107720385 modified "2023-10-16" @default.
• W2107720385 title "Autophagy Protects Against Aminochrome-Induced Cell Death in Substantia Nigra-Derived Cell Line" @default.
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• W2107720385 doi "https://doi.org/10.1093/toxsci/kfr060" @default.
• W2107720385 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3145404" @default.
• W2107720385 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21427056" @default.
• W2107720385 hasPublicationYear "2011" @default.
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