Leukotriene synthesis in response to A23187 is inhibited by methyl- beta-cyclodextrin in RBL-2H3 cells |
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Authors: | You Hye Jin Seo Ji-Min Moon Ji-Young Han Sung-Sik Ko Young-Gyu Kim Jae-Hong |
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Institution: | School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea. |
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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-beta-cyclodextrin (MbetaCD), 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 MbetaCD, and this effect was reversed when cholesterol was added. In an approach to identifying the MbetaCD-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. |
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