Leukotriene synthesis in response to A23187 is inhibited by methyl-β-cyclodextrin in RBL-2H3 cells

Hye Jin You, Ji Min Seo, Ji Young Moon, Sung Sik Han, Young Gyu Ko, Jae Hong Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Leukotrienes (LTs) are produced by several biosynthetic enzymes including cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LO), and 5-lipoxygenase activating protein (FLAP) in the perinuclear area. In the present study, we showed that pretreatment with methyl-β-cyclodextrin (MβCD), a cholesterol-depleting agent, dramatically reduced the synthesis of LTs in response to A23187 in mast cells. A23187-induced LT synthesis was inhibited by pretreatment with MβCD, and this effect was reversed when cholesterol was added. In an approach to identifying the MβCD-sensitive protein(s), we observed that FLAP co-localized with flotillin-1, a lipid raft marker protein, in the lipid raft-rich low-density region of sucrose gradients. In addition, electron microscopic analysis revealed that FLAP co-localized with flotillin-1. Together, these results suggest that FLAP is present in cholesterol-rich lipid raft-like domains and that its localization in these domains is critical for LT synthesis.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalMolecules and cells
Volume23
Issue number1
Publication statusPublished - 2007 Feb

Keywords

  • A23187
  • Cholesterol
  • FLAP
  • Leukotrienes
  • Lipid raft
  • Mast cell

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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