Active metabolism of arachidonic acid by Kaposi sarcoma cells cultured from lung biopsies (KS-3); identification by HPLC and MS/MS of the predominant metaboilte secreted as the 11,12-epoxy-eicosatrienoic acid |
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Authors: | Fernand Dray Brigitte Vulliez-Le Normand Alain Deroussent Isabelle Briquet Marie-Madeleine Gabellec Shuji Nakamura Larry M. Wahl Alain Gouyette Zaki S. Salahuddin |
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Affiliation: | 1. U207 INSERM, URIA Institut Pasteur, Paris, France;2. URA 158 C.N.R.S., Institut Gustave Roussy, Villejuif, France;3. Laboratory of Tumor Cell Biology, National Cancer Institute. NIH, Bethesda, MD, USA;4. Cellular Immunology Section, Laboratory of Immunology, National Instiute of Dental Research, NIH, Bethesda, MD, USA |
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Abstract: | The development of long-term culture of AIDS-KS cells has allowed us to investigate further a possible vascular origin of Kaposi sarcoma. Taking into account the relative specificity of arachidonic acid (AA) metabolism according to cell type, the AA ‘cascade’ was analyzed in cultured KS-3 cells established from lung biopsies and compared to human umbilical venous endothelial (H-UVE) cells and human myometrial smooth muscle (H-MSM) cells, under basal conditions and after stimulation with vasoactive agents such as histamine or thrombin. Considering strictly the ‘prostaglandin’ profile given by RIAs, the metabolism of AA was closer, whilst not identical, to H-UVE than to H-MSM cells. However, evaluation of all the eicosanoids released from [3H]AA labeled KS-3 cells revealed that the predominant metabolite was not prostacyclin (PGI2), as suggested from PG RIAs, but an epoxy-eicosatrienoic acid (EET), identified as the 11, 12 isomer by HPLC and MS/MS. The synthesis of this EET is probably cytochrome P-450 monooxygenase dependent. Its potential role in the development of the KS tumor cells is under investigation. |
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Keywords: | AIDS Kaposi sarcoma Arachidonic acid metabolism Epoxyeicosatrienoic acid KS Kaposi sarcoma AIDS acquired immune deficiency syndrome HTLV human T-cell lymphotropic virus H-UVE human umbilical venous endothelial H-MSM human myometrial smooth muscle FCS foetal calf serum PMA phorbol 12-myristate 13-acetate ETYA eicosatetraynoic acid Indo indomethacin Hist histamine Met metyapone DXM dexamethasone AA arachidonic acid PG prostaglandin prostacyclin TX thromboxane HETE hydroxyeicosatetraenoic acid LT leukotriene EET epoxyeicosatrienoic acid CO cyclooxygenase LO lipoxygenase rp-HPLC reverse-phase high-performance liquid chromatography rt retention time FAB fast atom bombardment MS/MS tandem mass spectrometry |
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