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 language | English |
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Pages (from-to) | 57-63 |
Number of pages | 7 |
Journal | Molecules and cells |
Volume | 23 |
Issue number | 1 |
Publication status | Published - 2007 Feb |
Keywords
- A23187
- Cholesterol
- FLAP
- Leukotrienes
- Lipid raft
- Mast cell
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology