Synthesis of cysteinyl leukotrienes in human endothelial cells: subcellular localization and autocrine signaling through the CysLT2 receptor - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue FASEB Journal Année : 2011

Synthesis of cysteinyl leukotrienes in human endothelial cells: subcellular localization and autocrine signaling through the CysLT2 receptor

Résumé

The purpose of this study was to characterize enzyme, receptor, and signaling involved in the synthesis and the activity of cysteinyl leukotrienes (cysLTs) in human umbilical vein endothelial cells (HUVECs). We used primary cultures of HUVECs and evaluated the formation of cys-LTs by RP-HPLC. Suicide inactivation and subcellular localization of the enzyme responsible for the conversion of leukotriene (LT) A4 into LTC4 were studied by repeated incubations with LTA4 and immunogold electron microscopy. The CysLT2 receptor in HUVECs was characterized by equilibrium binding studies, Western blot analysis, and immunohistochemistry. Concentration-response curves in HUVECs and in transfected COS-7 cells were used to characterize a novel specific CysLT2 receptor antagonist (pA2 of 8.33 and 6.79 against CysLT2 and CysLT1 receptors, respectively). The results obtained provide evidence that the mGST-II synthesizing LTC4 in HUVECs is pharmacologically distinguishable from the LTC4-synthase (IC50 of MK886 <5

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Chimie organique
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Dates et versions

hal-00628399 , version 1 (03-10-2011)

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Chiara Carmini, Maria Rosa Accomazzo, Emanuele Borroni, Laura Vitellaro-Zucarello, Thierry Durand, et al.. Synthesis of cysteinyl leukotrienes in human endothelial cells: subcellular localization and autocrine signaling through the CysLT2 receptor. FASEB Journal, 2011, 25, pp.3519-3528. ⟨10.1096/fj.10-177030⟩. ⟨hal-00628399⟩
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