Stimulation by de novo-synthesized ceramide of phospholipase A2-dependent cholesterol esterification promoted by the uptake of oxidized low-density lipoprotein in macrophages

Kazuyuki Kitatani, Megumi Nemoto, Satoshi Akiba, Takashi Sato

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

The involvement of cytosolic phospholipase A2 (cPLA2) and ceramide in the accumulation of cholesteryl ester induced by the uptake of oxidized low-density lipoproteins (oxLDL) in macrophages was investigated. Uptake of oxLDL by [3H]oleic acid-labeled macrophages stimulated the formation of cholesteryl oleate, and this process was completely inhibited by a cPLA2 inhibitor. Under the conditions, a time-dependent increase in ceramide was observed, while sphingomyelin levels were unaffected. The production of ceramide was completely inhibited by fumonisin B1, an inhibitor of the de novo synthesis of ceramide, and oxLDL-induced cholesteryl oleate formation was inhibited partially. Treatment of the cells with sphingomyelinase accelerated the formation of cholesteryl ester. Furthermore, sphingomyelinase or cell-permeable ceramide induced the release of oleic acid, and this was inhibited by a cPLA2 inhibitor. These results suggest that activation of cPLA2 is responsible for the formation of cholesteryl ester induced by the uptake of oxLDL in macrophages, and that de novo-synthesized ceramide is implicated, at least in part, in this process.

Original languageEnglish
Pages (from-to)695-701
Number of pages7
JournalCellular Signalling
Volume14
Issue number8
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Ceramide
  • Cholesteryl ester
  • Fumonisin B
  • Macrophage
  • Oleic acid
  • Oxidized low-density lipoprotein
  • Phospholipase A

ASJC Scopus subject areas

  • Cell Biology

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