Effects of tocotrienol on the intracellular translocation and degradation of apolipoprotein B: possible involvement of a proteasome independent pathway

Biochem Biophys Res Commun. 1998 May 29;246(3):640-3. doi: 10.1006/bbrc.1998.8677.


gamma-Tocotrienol (gamma-T3), a HMG CoA reductase inhibitor, was previously shown to stimulate the intracellular degradation of apolipoprotein B (apoB) in HepG2 cells. The aim of this study was to explore the effects of gamma-T3 on the proteasome dependent co-translational degradation and the proteasome independent post-translational degradation of apoB. Previous studies have shown that apoB translocation across the endoplasmic reticulum (ER) membrane governs the co-translational degradative pathway of apoB. Therefore, we first examined the effects of gamma-T3 on this pathway using a specific translocation assay derived from HepG2 cells. Our results indicated that gamma-T3 reduced the efficiency of apoB translocation across the ER membrane, suggesting that co-translational degradation may be partially involved. Evidence of an ER associated post-translational degradation was also provided upon pre-treating digitonin-permeabilized HepG2 cells with a proteasome inhibitor, lactacystin. When chased for 2h, ER degradation of apoB was observed and was further enhanced in the presence of gamma-T3 versus untreated control, in spite of proteasome inhibition. Combined with the ability of ALLN, a proteasome and cysteine protease inhibitor, to block the post-translational degradation of apoB, the data suggest that gamma-T3 diverted more apoB to a cytosolic proteasomal dependent and possibly an ER-associated proteasomal independent degradation pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives
  • Acetylcysteine / pharmacology
  • Apolipoproteins B / metabolism*
  • Biological Transport
  • Cell Membrane Permeability
  • Chromans / pharmacology*
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Leupeptins / pharmacology
  • Liver / metabolism*
  • Multienzyme Complexes / metabolism*
  • Proteasome Endopeptidase Complex
  • Protein Processing, Post-Translational
  • Tumor Cells, Cultured
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology


  • Apolipoproteins B
  • Chromans
  • Cysteine Proteinase Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Leupeptins
  • Multienzyme Complexes
  • acetylleucyl-leucyl-norleucinal
  • lactacystin
  • Vitamin E
  • plastochromanol 8
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Acetylcysteine