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Leukotriene Synthesis in Response to A23187 Is Inhibited by Methyl-β-Cyclodextrin in RBL-2H3 Cells  

You, Hye Jin (School of Life Sciences and Biotechnology, Korea University)
Seo, Ji-Min (School of Life Sciences and Biotechnology, Korea University)
Moon, Ji-Young (School of Life Sciences and Biotechnology, Korea University)
Han, Sung-Sik (School of Life Sciences and Biotechnology, Korea University)
Ko, Young-Gyu (School of Life Sciences and Biotechnology, Korea University)
Kim, Jae-Hong (School of Life Sciences and Biotechnology, Korea University)
Publication Information
Molecules and Cells / v.23, no.1, 2007 , pp. 57-63 More about this Journal
Abstract
Leukotrienes (LTs) are produced by several biosynthetic enzymes including cytosolic phospholipase $A_2$ ($cPLA_2$), 5-lipoxygenase (5-LO), and 5-lipoxygenase activating protein (FLAP) in the perinuclear area. In the present study, we showed that pretreatment with methyl-${\beta}$-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 M${\beta}$CD, and this effect was reversed when cholesterol was added. In an approach to identifying the $M{\beta}CD$-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.
Keywords
A23187; Cholesterol; FLAP; Leukotrienes; Lipid Raft; Mast Cell;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
Times Cited By Web Of Science : 5  (Related Records In Web of Science)
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