Stable Expression of Short Interfering RNA for DT-Diaphorase Induces Neurotoxicity
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2010-09Metadata
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Lozano, Jorge
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Stable Expression of Short Interfering RNA for DT-Diaphorase Induces Neurotoxicity
Abstract
DT-Diaphorase has been proposed to play a neuroprotective role in dopaminergic neurons by preventing
aminochrome neurotoxicity. There are several studies supporting this idea, but in all studies, we used
dicoumarol, an inhibitor of DT-diaphorase. We have designed and developed two siRNA to silence the
expression of DT-diaphorase to study its role in aminochrome metabolism. We transduced RCSN-3 cells
with retroviral particles containing a pRetroSuper plasmid coding a siRNA for DT-diaphorase. The cells
selected in the presence of puromycin generated a stable cell line RCSN-3Nq6 and RCSN-3Nq7 with
low expression of DT-diaphorase (27% and 33% of wild type, respectively). A significant cell death was
observed in RCSN-3 cells expressing siRNA Nq6 and Nq7 for DT-diaphorase when were incubated
with 100 μM aminochrome during 48 (4- and 3.5-fold, respectively; P < 0.01). These results support the
protective role of DT-diaphorase against aminochrome neurotoxicity in dopaminergic neurons containing
neuromelanin and show that Nq6 and Nq7 siRNA are very useful tools to study the role of DT-diaphorase
in aminochrome metabolism.
Patrocinador
This work was supported by FONDECYT
1061083 and 1100165 and FIRCA R03 TW07044-01.
Identifier
URI: https://repositorio.uchile.cl/handle/2250/128784
DOI: DOI: 10.1021/tx100182a
ISSN: 0893-228X
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CHEMICAL RESEARCH IN TOXICOLOGY Volume: 23 Issue: 9 Pages: 1492-1496 Published: SEP 2010
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