Neomycin inhibits secretion of apolipoprotein[a] by increasing retention on the hepatocyte cell surface

Robert E. Lanford, Larry Estlack, Ann L. White

    Research output: Contribution to journalArticle

    13 Scopus citations

    Abstract

    Neomycin therapy reduces plasma levels of low density lipoprotein and lipoprotein[a] (Lp[a]). To determine whether neomycin directly alters the biogenesis of Lp[a], we have examined the effect of neomycin on apolipoprotein[a] (apo[a]) synthesis and secretion in primary cultures of baboon hepatocytes. Using this system, we have previously shown that apo[a] is synthesized as a lower molecular weight precursor that upon maturation becomes associated with the cell surface before release into the culture medium. Treatment of hepatocytes with 10 mM neomycin reduced levels of apo[a] in the culture medium by as much as 12-fold. Although a portion of the reduced secretion could be accounted for by a reduction in total protein synthesis, the greatest effect of neomycin on apo[a] secretion was to decrease the release of mature apo[a] from the hepatocyte cell surface into the culture medium. Treatment of hepatocyte cultures with trypsin confirmed that mature apo[a] in neomycin-treated cells was still transported to the cell surface. Examination of related antibiotics demonstrated that inhibition of apo[a] secretion is a general property shared by the deoxystreptamine antibiotics. The mechanism by which neomycin affects the apo[a]-cell surface interaction is not known, but neomycin is known to perturb cell surface membranes, inhibit the interaction of some ligands with their cell surface receptors, and inhibit the metabolism of phosphatidylinositol 4,5 biphosphate. These studies suggest that cell surface association of apo[a] may play a role in Lp[a] biogenesis in vivo.

    Original languageEnglish (US)
    Pages (from-to)2055-2064
    Number of pages10
    JournalJournal of lipid research
    Volume37
    Issue number10
    StatePublished - Oct 1 1996

    Keywords

    • apolipoprotein B
    • lipoprotein[a]
    • phosphatidylinositol
    • primary hepatocytes
    • serum-free medium

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology
    • Cell Biology

    Fingerprint Dive into the research topics of 'Neomycin inhibits secretion of apolipoprotein[a] by increasing retention on the hepatocyte cell surface'. Together they form a unique fingerprint.

  • Cite this