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Titolo:
An anti-platelet agent, OPC-29030, inhibits translocation of 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid production in human platelets
Autore:
Ozeki, Y; Nagamura, Y; Ito, H; Unemi, F; Kimura, Y; Igawa, T; Kambayashi, J; Takahashi, Y; Yoshimoto, T;
Indirizzi:
Otsuka Pharmaceut Co Ltd, Thrombosis & Vasc Res Lab, Tokushima 7710192, Japan Otsuka Pharmaceut Co Ltd Tokushima Japan 7710192 okushima 7710192, Japan Otsuka Amer Pharmaceut Inc, Rockville, MD 20850 USA Otsuka Amer PharmaceutInc Rockville MD USA 20850 Rockville, MD 20850 USA Kanazawa Univ, Sch Med, Dept Pharmacol, Kanazawa, Ishikawa 9208640, Japan Kanazawa Univ Kanazawa Ishikawa Japan 9208640 wa, Ishikawa 9208640, Japan
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 8, volume: 128, anno: 1999,
pagine: 1699 - 1704
SICI:
0007-1188(199912)128:8<1699:AAAOIT>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
5-LIPOXYGENASE-ACTIVATING PROTEIN; 12S-HYDROXYEICOSATETRAENOIC ACID; MEMBRANE; LIPOXYGENASE; LEUKOTRIENES; INFLAMMATION; LEUKOCYTES; TARGET; CELLS; PLAYS;
Keywords:
OPC-29030; 12(S)-HETE; 5(S)-HETE; 12-lipoxygenase; 5-lipoxygenase; FLAP; platelet; translocation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Ozeki, Y Otsuka Pharmaceut Co Ltd, Thrombosis & Vasc Res Lab, 463-10 Kagasuno, Tokushima 7710192, Japan Otsuka Pharmaceut Co Ltd 463-10 Kagasuno Tokushima Japan 7710192
Citazione:
Y. Ozeki et al., "An anti-platelet agent, OPC-29030, inhibits translocation of 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid production in human platelets", BR J PHARM, 128(8), 1999, pp. 1699-1704

Abstract

1 In human platelets, arachidonic acid is mainly metabolized by the two enzyme systems; cyclooxygenase and 12-lipoxygenase. Cyclo-oxygenase produces prostaglandin H-2 which is further converted to thromboxane B-2. 12-Lipoxygenase synthesizes 12(S)-hydroperoxyeicosatetraenoic acid which is reduced to 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE).2 An anti-platelet compound, OPC-29030, dose-dependently inhibited 12(S)-HETE production with an IC50 of 0.06 +/- 0.01 mu M, but not synthesis of thromboxane Bz in human platelets. Although the compound suppressed 12(S)-HETEproduction in human platelets, cytosolic 12-lipoxygenase activity was not inhibited up to 10 mu M. Essentially identical data were obtained with a 12-lipoxygenase of human erythroleukaemia cells which had megakaryocyte/platelet-like properties.3 OPC-29030 also suppressed production of S(S)-HETE, a 5-lipoxygenase product, in rat basophilic leukaemia cells without inhibiting enzyme activity. It has been shown that 5-lipoxygenase binds to membrane 5-lipoxygenase-activating protein (FLAP) to produce S(S)-HETE, and thus FLAP inhibitor suppresses cellular S(S)-HETE production.4 A FLAP inhibitor, L-655,238, suppressed platelet IZ(S)-HETE production, but had no effect on the 12-lipoxygenase activity.5 Western blot analysis showed that platelet 12-lipoxygenase translocated from cytosol to membranes upon thrombin stimulation, and OPC-29030 suppressed this process in a dose-dependent manner.6 These results suggest that the 12-lipoxygenase of human platelets binds to FLAP or a similar protein, and OPC-29030 suppresses IZ(S)-HETE production by inhibiting a certain step of the 12-lipoxygenase translocation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 06:06:33