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Stimulation by de novo-synthesized ceramide of phospholipase A(2)-dependent cholesterol esterification promoted by the uptake of oxidized low-density lipoprotein in macrophages.

Abstract：

:The involvement of cytosolic phospholipase A(2) (cPLA(2)) 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 [(3)H]oleic acid-labeled macrophages stimulated the formation of cholesteryl oleate, and this process was completely inhibited by a cPLA(2) 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 cPLA(2) inhibitor. These results suggest that activation of cPLA(2) 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.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Kitatani K,Nemoto M,Akiba S,Sato T

doi

10.1016/s0898-6568(02)00014-1

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

695-701

issue

8

eissn

0898-6568

issn

1873-3913

pii

S0898656802000141

journal_volume

14

pub_type

杂志文章

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