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Neurotoxicity Research

, Volume 35, Issue 1, pp 255–259 | Cite as

DT-Diaphorase Prevents Aminochrome-Induced Lysosome Dysfunction in SH-SY5Y Cells

  • Catalina Meléndez
  • Patricia Muñoz
  • Juan Segura-AguilarEmail author
ORIGINAL ARTICLE
  • 38 Downloads

Abstract

Aminochrome has been reported to induce lysosomal dysfunction by inhibiting the vacuolar H-type ATPase localized in lysosome membrane. DT-diaphorase has been proposed to prevent aminochrome neurotoxicity but it is unknown whether this enzyme prevents aminochrome-induced lysosomal dysfunction. In the present study, we tested the protective role of DT-diaphorase in lysosomal dysfunction by generating a cell line (SH-SY5YsiNQ7) with a stable expression of a siRNA against DT-diaphorase with only 10% expression of mRNA enzyme. The cells differentiated with retinoic acid and 12-o-tetradecanoylphorbol-13-acetate show a significant increase in the expression of tyrosine hydroxylase, vesicular monoamine transporter-2, and dopamine transporter. The incubation of SH-SY5YsiNQ7 cells with 10 μM aminochrome resulted in a significant decrease of lysosome pH determined by using acridine orange, while aminochrome has no effect on SH-SY5Y cells. These results support the proposed protective role of DT-diaphorase against aminochrome-induced lysosomal dysfunction.

Keywords

DT-Diaphorase Lysosomal dysfunction Aminochrome Dopamine Neurotoxicity Neuroprotection 

Notes

Funding

This research was supported by FONDECYT (1170033).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that there is no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Catalina Meléndez
    • 1
  • Patricia Muñoz
    • 1
    • 2
  • Juan Segura-Aguilar
    • 1
    Email author
  1. 1.Molecular and Clinical Pharmacology, ICBM, Faculty of MedicineUniversity of ChileSantiagoChile
  2. 2.Instituto de Ciencias Biomédicas, Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

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