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Biochem Biophys Res Commun. 1998 May 29;246(3):640-3.

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

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1
Division of Medical Technology, University of Hawaii at Manoa, Honolulu 96822, USA.

Abstract

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.

PMID:
9618265
DOI:
10.1006/bbrc.1998.8677
[Indexed for MEDLINE]

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