DOI: 10.1007/s12640-017-9747-4 Pages: 1-6
Article Type: ORIGINAL ARTICLE

DT-diaphorase Protects Against Autophagy Induced by Aminochrome-Dependent Alpha-Synuclein Oligomers

1. University of Chile, Molecular and Clinical Pharmacology, ICBM, Faculty of Medicine

Correspondence to:
Patricia S. Muñoz
Tel: +56 229786637
Email: bioquimica.pams@gmail.com

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Abstract

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.

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  • Accepted: Apr 10, 2017
  • Online: May 6, 2017
  • Revised: Apr 6, 2017

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