title: Inhibition of translocation of nascent apolipoprotein B across the endoplasmic reticulum membrane is associated with selective inhibition of the synthesis of apolipoprotein B.
abstract: In HepG2 cells, inhibition of apolipoprotein B100 (apoB) translocation across the endoplasmic reticulum by an microsomal triglyceride transfer protein (MTP) inhibitor (CP-10447) in the presence of N-acetyl-leucinyl-norleucinal, a proteasomal inhibitor, results in accumulation of newly synthesized apoB in the translocation channel. Here we demonstrated that such accumulation led to a specific reduction of apoB synthesis. ApoB mRNA levels remained unchanged, but we observed reduced rates of elongation of nascent apoB in puromycin-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 translocation arrest of apoB in the endoplasmic reticulum channel can exert a selective and negative effect on the synthesis of apoB at the stage of elongation.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pan
authors.forename: J s
authors.initials: Js
authors.lastname: Liang
authors.forename: E A
authors.initials: EA
authors.lastname: Fisher
authors.forename: H N
authors.initials: HN
authors.lastname: Ginsberg
mesh_terms: D001055:Apolipoproteins B / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008702:Methaqualone / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
chemical_list: C102576:4-bromomethaqualone; D001055:Apolipoproteins B; D002352:Carrier Proteins; D007976:Leupeptins; D012333:RNA, Messenger; C106092:microsomal triglyceride transfer protein; C063261:acetylleucyl-leucyl-norleucinal; D008702:Methaqualone