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DT-diaphorase protects against autophagy induced by aminochrome dependent alpha synuclein oligomers

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2017
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Muñoz, Patricia S.
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DT-diaphorase protects against autophagy induced by aminochrome dependent alpha synuclein oligomers
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  • Muñoz, Patricia S.;
  • Segura Aguilar, Juan;
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 mu M aminochrome and 10 mu M rapamycin followed by a decrease in cell death compared to RCSN-3 cells incubated with 20 mu M aminochrome alone. The incubation of RCSN-3NQ7SNCA cells with 20 mu M aminochrome and 10 mu M rapamycin does not change the expression of LC3-II in comparison with RCSN-3NQ7SNCA cells incubated with 20 mu M aminochrome alone. The incubation of both cell lines preincubated with 100 nM bafilomycin and 20 mu M 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 mu M aminochrome. These results support the protective role of DT-diaphorase against SNCA oligomers-induced autophagy inhibition.
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FONDECYT 1100165
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Artículo de publicación ISI
 
Artículo de publicación SCOPUS
 
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URI: https://repositorio.uchile.cl/handle/2250/149728
DOI: 10.1007/s12640-017-9747-4
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Neurotoxicity Research 32(3): 362-367
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