Low density lipoprotein receptor degradation is influenced by a mediator protein(s) with a rapid turnover rate, but is unaffected by receptor up- or down-regulation

L. A.F. Casciola, D. R. Van Der Westhuyzen, W. Gevers, G. A. Coetzee

Research output: Contribution to journalArticlepeer-review

Abstract

Treatment of cultured human skin fibroblasts with cycloheximide retarded the down-regulation of low density lipoprotein (LDL) receptor activity caused by 25-hydroxycholesterol. The rate of LDL receptor degradation, measured directly by means of [35S]methionine pulse-chase experiments, was also markedly inhibited by cycloheximide (or puromycin), suggesting that continuous synthesis of a short-lived mediator protein(s) was necessary for normal LDL receptor turnover. In the absence of cycloheximide, both the up- and down-regulation of LDL receptor activity took place with a half-time of approximately 12 hr. Pulse-chase measurements with [35S]methionine yielded a receptor half-life (t 1/2 ) of 11.7 ± 2.2 hr (n = 10) in up-regulated cells; the t 1/2 in the partially down-regulated state was similar. The presence of LDL or 25-hydroxycholesterol did not alter this degradation rate. Regulation of LDL receptor activity under these various culture conditions therefore probably occurred solely as a result of changes in the rate of receptor synthesis. The cycloheximide-sensitive factor(s) that influences receptor turnover apparently did not play a regulatory role in the up- or down-regulation of the LDL receptor.

Original languageEnglish (US)
Pages (from-to)1481-1489
Number of pages9
JournalJournal of Lipid Research
Volume29
Issue number11
StatePublished - 1988
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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