Regulation of sterol carrier protein 2 (SCP2) gene expression in rat peritoneal macrophages during foam cell formation. A key role for free cholesterol content

A. Hirai, T. Kino, K. Tokinaga, K. Tahara, Y. Tamura, S. Yoshida

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Sterol carrier protein 2 (SCP2) has been shown to be involved in intracellular transport and metabolism of cholesterol. However, there have been no reports concerning SCP2 in macrophages, the major source of atheromatous foam cells. We investigated whether SCP2 is present in rat peritoneal macrophages and determined the changes of SCP2 and its mRNA levels in macrophages during foam cell formation induced by acetylated LDL (AcLDL). Immunoblot analysis and Northern blot analysis demonstrated that both SCP2 and its mRNA are expressed in rat peritoneal macrophages. Incubations with AcLDL caused a dose- and time-dependent increase of cellular esterified cholesterol, SCP2 and its mRNA in rat peritoneal macrophages. The inhibitor of acyl-CoA:cholesterol acyltransferase further enhanced AcLDL- induced increase of SCP2 protein and its mRNA. Incubations with 25-hydroxy cholesterol also caused a dose-dependent stimulation of SCP2 gene expression in macrophages, while incubation with maleylated BSA had no effect. These results suggest that the increment of cellular-free cholesterol is responsible for enhanced SCP2 gene expression in macrophages. The enhancement of SCP2 gene expression by AcLDL suggests that SCP2 may play an important role during foam cell formation induced by AcLDL which may be most important step for the atherosclerosis.

Original languageEnglish
Pages (from-to)2215-2223
Number of pages9
JournalJournal of Clinical Investigation
Volume94
Issue number6
DOIs
Publication statusPublished - 1 Jan 1994

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Keywords

  • acetylated LDL
  • foam cell
  • macrophage
  • oxysterol
  • sterol carrier protein 2

ASJC Scopus subject areas

  • Medicine(all)

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