TIEG1 facilitates transforming growth factor-beta-mediated apoptosis in the oligodendroglial cell line OLI-neu

J Neurosci Res. 2004 Feb 1;75(3):344-52. doi: 10.1002/jnr.10856.

Abstract

Transforming growth factor-beta (TGF-beta) plays an important role during the period of developmental cell death in the nervous system. Using the oligodendroglial precursor cell line OLI-neu, we have previously established an in vitro system to analyze TGF-beta-mediated cell death on the molecular level. We could show that the Krüppel-like Zn-finger transcription factor TIEG1 was up-regulated after TGF-beta stimulation of OLI-neu cells and mimicked TGF-beta effects in these cells; i.e., overexpression of TIEG1 in OLI-neu cells induced apoptosis as shown by apoptosis ELISA, DNA fragmentation, and caspases-3 activation. The apoptotic pathway seemed to be initiated by repressing the expression of the antiapoptotic protein Bcl-XL. In contrast, the reporter activity of a SMAD consensus promoter was induced, whereas the promoter activity of the inhibitory SMAD7 was reduced, suggesting that SMAD-dependent TGF-beta responses, such as TGF-beta-induced apoptosis, are enhanced in the presence of TIEG1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Blotting, Western
  • Carrier Proteins / metabolism
  • Caspase 3
  • Caspases / metabolism
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Mice
  • Oligodendroglia / pathology
  • Oligodendroglia / physiology*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smad Proteins
  • Trans-Activators / physiology
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation
  • bcl-X Protein

Substances

  • Apoptosis Regulatory Proteins
  • Bcl2l1 protein, mouse
  • Carrier Proteins
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Smad Proteins
  • TP53BP2 protein, human
  • Tieg1 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Transforming Growth Factor beta
  • bcl-X Protein
  • CASP3 protein, human
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases