Effects of tunicamycin on the binding and degradation of low density lipoproteins and glycoprotein synthesis in cultured human fibroblasts

S. Chatterjee, P. O. Kwiterovich, C. S. Sekerke

Research output: Contribution to journalArticle

Abstract

Tunicamycin, an antibiotic that prevents the glycosylation of newly synthesized protein, was found to inhibit the high affinity binding and degradation of 125I-low density lipoproteins in normal human cultured fibroblasts. This inhibition of the binding and degradation of low density lipoproteins was time-dependent and was reversible upon removal of tunicamycin from the medium. Glycoprotein synthesis was inhibited more than 74% in tunicamycin-treated cells, while protein synthesis was minimally inhibited. After tunicamycin was removed from the medium, incubation of the cells in medium supplemented with lipoprotein-deficient serum for 24 to 48 hr reversed the inhibitory effect of the antibiotic on both glycoprotein synthesis and the binding and degradation of 125I-low density lipoproteins. These observations indicate that there is a relationship between glycoprotein synthesis and the binding and degradation of low density lipoproteins. Glycosylation of the receptor for low density lipoproteins may be necessary for its intracellular migration or for its normal orientation on the cell surface. Alternatively, the glycosylation of an intracellular or cell surface glycoprotein(s) may be necessary in order for the receptor for low density lipoprotein to function normally. Since tunicamycin blocks the synthesis of N-acetylglucosaminyl pyrophosphoryl polyisoprenol and results in the synthesis of glycoproteins deficient in asparagine-linked oligosaccharide, the data further suggest a possible role of polyisoprenyl compounds in the synthesis of glycoproteins in cultured human fibroblasts. The possible role of this pathway in a feedback regulation of the receptor by low density lipoproteins remains to be elucidated.

Original languageEnglish (US)
Pages (from-to)3704-3707
Number of pages4
JournalJournal of Biological Chemistry
Volume254
Issue number10
StatePublished - Dec 1 1979

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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