tailieunhanh - Báo cáo khoa học: Cholesterol and its anionic derivatives inhibit 5-lipoxygenase activation in polymorphonuclear leukocytes and MonoMac6 cells

5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of leukotrie-nes (LTs), biological mediators of host defense reactions and of inflamma-tory diseases. While the role of membrane binding in the regulation of 5-LO activity is well established, the effects of lipids on cellular activity when added to the medium has not been characterized. | iFEBS Journal Cholesterol and its anionic derivatives inhibit 5-lipoxygenase activation in polymorphonuclear leukocytes and MonoMac6 cells Dmitry A. Aleksandrov1 Anna N. Zagryagskaya1 Marina A. Pushkareva1 Markus Bachschmid2 Marc Peters-Golden3 Oliver Werz4 Dieter Steinhilber4 and Galina F. Sud ina1 1 . Belozersky Institute of PhysicochemicalBiology Moscow State University Russia 2 Faculty of Biology University of Konstanz Germany 3 Pulmonary and CriticalCare Medicine Division University of Michigan Ann Arbor USA 4 Institute of PharmaceuticalChemistry ZAFES University of Frankfurt Germany Keywords 5-lipoxygenase cholesterol sulfate leukotrienes neutrophil Correspondence G. F. Sud ina . Belozersky Institute of PhysicochemicalBiology Moscow State University Russia Fax 7 095 9393181 Tel 7 095 9393184 E-mail sudina@ Received 19 September 2005 revised 23 November 2005 accepted 5 December 2005 doi 5-Lipoxygenase 5-LO is the key enzyme in the biosynthesis of leukotrienes LTs biological mediators of host defense reactions and of inflammatory diseases. While the role of membrane binding in the regulation of 5-LO activity is well established the effects of lipids on cellular activity when added to the medium has not been characterized. Here we show such a novel function of the most abundant sulfated sterol in human blood cholesterol sulfate CS to suppress LT production in human polymorphonuclear leukocytes PMNL and Mono Mac6 cells. We synthesized another anionic lipid cholesterol phosphate which demonstrated a similar capacity in suppression of LT synthesis in PMNL. Cholesteryl acetate was without effect. Cholesterol increased the effect of CS on 5-LO product synthesis. CS and cholesterol also inhibited arachidonic acid AA release from PMNL. Addition of exogenous AA increased the threshold concentration of CS required to inhibit LT synthesis. The effect of cholesterol and its anionic derivatives can arise from remodeling .

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