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Induction of the protective antioxidant response element pathway by 6-hydroxydopamine in vivo and in vitro.

Publication ,  Journal Article
Jakel, RJ; Kern, JT; Johnson, DA; Johnson, JA
Published in: Toxicol Sci
September 2005

Parkinson's disease, a progressive neurodegenerative disorder, is characterized by loss of midbrain dopaminergic neurons. The etiology of sporadic Parkinson's disease is unknown; however, oxidative stress is thought to play a major role in disease pathogenesis. Little is known regarding the transcriptional changes that occur in Parkinson's disease. The antioxidant response element is a cis-acting enhancer sequence that is upstream of many phase II detoxification and antioxidant genes. Here we show that 6-hydroxydopamine, a mitochondrial inhibitor used to model Parkinson's disease, activates the antioxidant response element both in cultured neurons and in the striatum and brainstem of 6-OHDA-lesioned mice. Pretreatment with antioxidants or NMDA receptor antagonists reduced but did not abolish activation. Further induction of this pathway with tert-butylhydroquinone was able to significantly reduce cell death due to 6-OHDA in vitro. These observations indicate that 6-OHDA activates the antioxidant response element through components of oxidative stress, excitotoxicity, and potential structural factors. Further induction of this endogenous defense mechanism may suggest a novel therapeutic venue in Parkinson's disease.

Duke Scholars

Published In

Toxicol Sci

DOI

ISSN

1096-6080

Publication Date

September 2005

Volume

87

Issue

1

Start / End Page

176 / 186

Location

United States

Related Subject Headings

  • Trans-Activators
  • Toxicology
  • Response Elements
  • Receptors, N-Methyl-D-Aspartate
  • Parkinson Disease
  • Oxidopamine
  • Oxidative Stress
  • NF-E2-Related Factor 2
  • Mice
  • Hydroquinones
 

Citation

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Jakel, R. J., Kern, J. T., Johnson, D. A., & Johnson, J. A. (2005). Induction of the protective antioxidant response element pathway by 6-hydroxydopamine in vivo and in vitro. Toxicol Sci, 87(1), 176–186. https://doi.org/10.1093/toxsci/kfi241
Jakel, Rebekah J., Jonathan T. Kern, Delinda A. Johnson, and Jeffrey A. Johnson. “Induction of the protective antioxidant response element pathway by 6-hydroxydopamine in vivo and in vitro.Toxicol Sci 87, no. 1 (September 2005): 176–86. https://doi.org/10.1093/toxsci/kfi241.
Jakel RJ, Kern JT, Johnson DA, Johnson JA. Induction of the protective antioxidant response element pathway by 6-hydroxydopamine in vivo and in vitro. Toxicol Sci. 2005 Sep;87(1):176–86.
Jakel, Rebekah J., et al. “Induction of the protective antioxidant response element pathway by 6-hydroxydopamine in vivo and in vitro.Toxicol Sci, vol. 87, no. 1, Sept. 2005, pp. 176–86. Pubmed, doi:10.1093/toxsci/kfi241.
Jakel RJ, Kern JT, Johnson DA, Johnson JA. Induction of the protective antioxidant response element pathway by 6-hydroxydopamine in vivo and in vitro. Toxicol Sci. 2005 Sep;87(1):176–186.
Journal cover image

Published In

Toxicol Sci

DOI

ISSN

1096-6080

Publication Date

September 2005

Volume

87

Issue

1

Start / End Page

176 / 186

Location

United States

Related Subject Headings

  • Trans-Activators
  • Toxicology
  • Response Elements
  • Receptors, N-Methyl-D-Aspartate
  • Parkinson Disease
  • Oxidopamine
  • Oxidative Stress
  • NF-E2-Related Factor 2
  • Mice
  • Hydroquinones