Decreased expression of bcl-2 and bcl-x mRNA coincides with apoptosis following intracerebral administration of 3-nitropropionic acid

Shuzo Sato, Glenn T. Gobbel, Jari Honkaniemi, Yibing Li, Takeo Kondo, Kensuke Murakami, Minako Sato, Jean Christophe Copin, Frank R Sharp, Pak H. Chan

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The mitochondrial toxin, 3-nitropropionic acid (3-NP), is an irreversible inhibitor of succinate dehydrogenase that induces apoptosis in vitro and in vivo. We injected 3-NP into the striatum of rats to examine the potential role of Bcl-2 or Bcl-x, proteins that can inhibit apoptosis, in brain injury due to 3-NP. Electrophoretic examination of striatal tissue indicated that 3-NP induced internucleosomal fragmentation typical of apoptosis. There was also histologic evidence of apoptosis based on staining by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) method. Apoptosis was first observed 6 h after injection, was maximal at 1 day, and was still observed on day 7. Expression of bcl-2, bcl-x, and c-jun mRNA expression was evaluated 1, 3, 6, and 12 h and 1, 3, 5, and 7 days after injection using in situ hybridization. Both bcl-2 and bcl-x mRNA expression in the striatum decreased starting at 6 h and continued to 5 days after injection. This was in contrast to an apparent increase in c-jun expression. The similarity in the time course of apoptosis to that of suppression of bcl-2 and bcl-x mRNA suggests that changes in expression of these genes may contribute to apoptosis following 3-NP injection.

Original languageEnglish (US)
Pages (from-to)56-64
Number of pages9
JournalBrain Research
Volume808
Issue number1
DOIs
StatePublished - Oct 12 1998
Externally publishedYes

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Keywords

  • 3-Nitropropionic acid
  • Apoptosis
  • bcl- 2
  • bcl-x
  • c-jun
  • Huntington's disease
  • Mitochondria

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sato, S., Gobbel, G. T., Honkaniemi, J., Li, Y., Kondo, T., Murakami, K., Sato, M., Copin, J. C., Sharp, F. R., & Chan, P. H. (1998). Decreased expression of bcl-2 and bcl-x mRNA coincides with apoptosis following intracerebral administration of 3-nitropropionic acid. Brain Research, 808(1), 56-64. https://doi.org/10.1016/S0006-8993(98)00784-7