Clofibrate and other peroxisomal proliferating agents relatively specifically inhibit synthesis of ethanolamine phosphoglycerides in cultured human fibroblasts

P. C. Thorne, D. M. Byers, F. B.St C. Palmer, H. W. Cook

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Effects of several classes of peroxisomal proliferators on peroxisomal functions, hepatomegaly, hepatocarcinogenesis and lipid metabolism have been extensively investigated in rodents. Less is known about influences of these agents, some used as hypolipidemic drugs, on various metabolic parameters in humans. We examined effects of clofibrate, di(2-ethyl-hexyl)phthalate (DEHP) and pirinixic acid (WY-14,643) on phospholipid metabolism in human fibroblasts in culture. Clofibrate inhibited incorporation of [1-14C]chexadecanol and clinolenic acid into ethanolamine phosphoglycerides in a time- and concentration-dependent manner; labeling of plasmalogens and non-plasmalogen ethanolamine phosphoglycerides was reduced by 40-80% compared to a generalized 10-30% inhibition of labeling of other phospholipids, including phosphatidylcholine. In pulse and pulse-chase experiments, selective inhibition of incorporation of [1,2-14C]ethanolamine, compared to [methyl-3H]choline, confirmed relative specificity of inhibition of ethanolamine phosphoglycerides. Similar concentration dependence and specificity for inhibition of phospholipid turnover was observed for DEHP and WY-14,643, in both control and mutant (Zeilweger and adrenoleukodystrophy) fibroblasts, in the absence of major effects on peroxisomal markers. These observations that peroxisomal proliferators specifically inhibit ethanolamine phosphoglyceride turnover in human fibroblasts should be considered when assessing the efficacy and safety of such agents as hypolipidemic drugs or when evaluating mechanisms of proliferator action at the cellular level.

Original languageEnglish
Pages (from-to)161-170
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1214
Issue number2
DOIs
Publication statusPublished - Sept 15 1994

Bibliographical note

Funding Information:
This work was supportedb y a Program Grant (PG-16)f rom the Medical ResearchC ouncil of Canadaa nd by a studentshipf rom the Dalhousie Medical Faculty Research Committee, Dalhousie University, Halifax, NS. The skilled technicala ssistanceo f Robert Zwicker, Susan Powell and Dr. Susan Thomas is gratefully acknow~edged.

ASJC Scopus Subject Areas

  • Biophysics
  • Biochemistry
  • Endocrinology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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