Inhibition of translocation of nascent apolipoprotein B across the endoplasmic reticulum membrane is associated with selective inhibition of the synthesis of apolipoprotein B
M. Pan et al., Inhibition of translocation of nascent apolipoprotein B across the endoplasmic reticulum membrane is associated with selective inhibition of the synthesis of apolipoprotein B, J BIOL CHEM, 275(35), 2000, pp. 27399-27405
In HepG2 cells, inhibition of apolipoprotein B100 (apoB) translocation acro
ss the endoplasmic reticulum by an microsomal triglyceride transfer protein
(MTP) inhibitor (CP-10447) in the presence of N-acetyl-leucinyl-norleucina
l, a proteasomal inhibitor, results in accumulation of newly synthesized ap
oB in the translocation channel. Here we demonstrated that such accumulatio
n led to a specific reduction of apoB synthesis. ApoB mRNA levels remained
unchanged, but we observed reduced rates of elongation of nascent apoB in p
uromycin-synchronized cells pretreated with MTP inhibitor. This observation
was consistent with a longer half-ribosome transit time for the synthesis
of apoB in MTP-inhibited cells. Initiation of translation of apoB mRNA was
not impaired by MTP inhibition. Overall, these findings suggest that transl
ocation arrest of apoB in the endoplasmic reticulum channel can exert a sel
ective and negative effect on the synthesis of apoB at the stage of elongat
ion.