Skip to main content
Journal cover image

Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line.

Publication ,  Journal Article
Paris, I; Muñoz, P; Huenchuguala, S; Couve, E; Sanders, LH; Greenamyre, JT; Caviedes, P; Segura-Aguilar, J
Published in: Toxicol Sci
June 2011

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.

Duke Scholars

Published In

Toxicol Sci

DOI

EISSN

1096-0929

Publication Date

June 2011

Volume

121

Issue

2

Start / End Page

376 / 388

Location

United States

Related Subject Headings

  • Vinblastine
  • Toxicology
  • Substantia Nigra
  • Sirolimus
  • Rats
  • Nerve Degeneration
  • NAD(P)H Dehydrogenase (Quinone)
  • Mitochondria
  • Microscopy, Electron, Transmission
  • Membrane Potential, Mitochondrial
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Paris, I., Muñoz, P., Huenchuguala, S., Couve, E., Sanders, L. H., Greenamyre, J. T., … Segura-Aguilar, J. (2011). Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line. Toxicol Sci, 121(2), 376–388. https://doi.org/10.1093/toxsci/kfr060
Paris, Irmgard, Patricia Muñoz, Sandro Huenchuguala, Eduardo Couve, Laurie H. Sanders, John Timothy Greenamyre, Pablo Caviedes, and Juan Segura-Aguilar. “Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line.Toxicol Sci 121, no. 2 (June 2011): 376–88. https://doi.org/10.1093/toxsci/kfr060.
Paris I, Muñoz P, Huenchuguala S, Couve E, Sanders LH, Greenamyre JT, et al. Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line. Toxicol Sci. 2011 Jun;121(2):376–88.
Paris, Irmgard, et al. “Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line.Toxicol Sci, vol. 121, no. 2, June 2011, pp. 376–88. Pubmed, doi:10.1093/toxsci/kfr060.
Paris I, Muñoz P, Huenchuguala S, Couve E, Sanders LH, Greenamyre JT, Caviedes P, Segura-Aguilar J. Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line. Toxicol Sci. 2011 Jun;121(2):376–388.
Journal cover image

Published In

Toxicol Sci

DOI

EISSN

1096-0929

Publication Date

June 2011

Volume

121

Issue

2

Start / End Page

376 / 388

Location

United States

Related Subject Headings

  • Vinblastine
  • Toxicology
  • Substantia Nigra
  • Sirolimus
  • Rats
  • Nerve Degeneration
  • NAD(P)H Dehydrogenase (Quinone)
  • Mitochondria
  • Microscopy, Electron, Transmission
  • Membrane Potential, Mitochondrial