sirolimus and aminochrome-1

sirolimus has been researched along with aminochrome-1* in 2 studies

Other Studies

2 other study(ies) available for sirolimus and aminochrome-1

ArticleYear
DT-diaphorase Protects Against Autophagy Induced by Aminochrome-Dependent Alpha-Synuclein Oligomers.
    Neurotoxicity research, 2017, Volume: 32, Issue:3

    Alpha-synuclein (SNCA) oligomers have been reported to inhibit autophagy. Aminochrome-induced SNCA oligomers are neurotoxic, but the flavoenzyme DT-diaphorase prevents both their formation and their neurotoxicity. However, the possible protective role of DT-diaphorase against autophagy impairment by aminochrome-induced SNCA oligomers remains unclear. To test this idea, we used the cell line RCSN-3NQ7SNCA, with constitutive expression of a siRNA against DT-diaphorase and overexpression SNCA, and RCSN-3 as control cells. A significant increase in LC3-II expression was observed in RCSN-3 cells treated with 20 μM aminochrome and 10 μM rapamycin followed by a decrease in cell death compared to RCSN-3 cells incubated with 20 μM aminochrome alone. The incubation of RCSN-3NQ7SNCA cells with 20 μM aminochrome and 10 μM rapamycin does not change the expression of LC3-II in comparison with RCSN-3NQ7SNCA cells incubated with 20 μM aminochrome alone. The incubation of both cell lines preincubated with 100 nM bafilomycin and 20 μM aminochrome increases the level of LC3-II. Under the same conditions, cell death increases in both cell lines in comparison with cells incubated with 20 μM aminochrome. These results support the protective role of DT-diaphorase against SNCA oligomers-induced autophagy inhibition.

    Topics: alpha-Synuclein; Animals; Autophagy; Cell Line; Cell Survival; Gene Expression; HEK293 Cells; Humans; Indolequinones; Macrolides; Microtubule-Associated Proteins; NAD(P)H Dehydrogenase (Quinone); Nerve Degeneration; Neuroprotection; Rats; RNA, Small Interfering; Sirolimus

2017
Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line.
    Toxicological sciences : an official journal of the Society of Toxicology, 2011, Volume: 121, Issue:2

    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.

    Topics: Animals; Autophagy; Caspase 3; Cell Death; Cell Line; Cytochromes c; DNA, Mitochondrial; Indolequinones; Melanins; Membrane Potential, Mitochondrial; Microscopy, Electron, Transmission; Mitochondria; NAD(P)H Dehydrogenase (Quinone); Nerve Degeneration; Rats; Sirolimus; Substantia Nigra; Vinblastine

2011