Growth arrest and DNA damage-inducible gene 153 increases transiently in the thalamus following focal cerebral infarction

Brain Res Mol Brain Res. 2005 Apr 4;134(2):189-97. doi: 10.1016/j.molbrainres.2004.10.029. Epub 2004 Nov 23.

Abstract

The thalamus degenerates following cerebral infarction in the territory supplied by the middle cerebral artery (MCA), and apoptosis is suspected to be the mechanism of this phenomenon. The author studied the role of the growth arrest and DNA damage-inducible gene (GADD) 153 in this thalamic degeneration. The MCA was occluded in stroke-prone spontaneously hypertensive rats. The expression of GADD 153 and Bcl-2, and the release of cytochrome c from the mitochondria to cytosol, were examined in the thalamus until 7 days after ischemia using in situ hybridization, immunoblot, immunohistochemistry and RT-PCR analyses. Gadd153 mRNA expression and GADD153 protein increased transiently at 2, 3, 5 and 7 days, and at 3 and 5 days after ischemia. Bcl-2 mRNA expression and Bcl-2 protein decreased at 3 and 5 days. The release of cytochrome c from the mitochondria was detected at 5 days. These results suggest that increased GADD 153 suppresses Bcl-2 expression, which causes the release of cytochrome c from the mitochondria and leads to thalamic degeneration.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Autoradiography
  • Blotting, Western / methods
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • Cerebral Infarction / etiology
  • Cerebral Infarction / metabolism*
  • Cytochromes c / metabolism
  • Cytosol / metabolism
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Infarction, Middle Cerebral Artery / complications
  • Male
  • Mitochondria / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Inbred SHR
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Thalamus / metabolism*
  • Time Factors
  • Transcription Factor CHOP
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • bcl-2-Associated X Protein

Substances

  • CCAAT-Enhancer-Binding Proteins
  • Ddit3 protein, rat
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Transcription Factors
  • bcl-2-Associated X Protein
  • Transcription Factor CHOP
  • Cytochromes c