Inhibition of N-formylmethionyl-leucyl-phenylalanine-stimulated tyrosine phosphorylation and phospholipase D activation by quercetin in rabbit neutrophils

被引:20
作者
Takemura, OS [1 ]
Banno, Y [1 ]
Nozawa, Y [1 ]
机构
[1] GIFU UNIV,SCH MED,DEPT BIOCHEM,GIFU 500,JAPAN
关键词
quercetin; bioflavonoids; neutrophils; superoxide production; phospholipase D; tyrosine phosphorylation;
D O I
10.1016/S0006-2952(97)00067-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We investigated the effect of bioflavonoid quercetin on tyrosine phosphorylation and phospholipase D (PLD, EC 3.1.4.4) activation in rabbit peritoneal neutrophils stimulated by N-formylmethionyl-leucylphenylalanine (fMLP). The quercetin dose-dependently inhibited degranulation and superoxide production in fMLP stimulated neutrophils. A strong inhibitory effect of quercetin on the tyrosine phosphorylation of several proteins (40, 42, 43, 45, 46 and 75 kDa) was observed when the neutrophils were pretreated with different concentrations of quercetin. Furthermore, quercetin inhibited mitogen activated protein kinase (MAP kinase) and PLD activation induced by fMLP in a dose-dependent manner. The reduction in PLD activity was 30% at 0.1 mu M and 70% at 100 mu M of quercetin. These results suggest that impairment of neutrophil functions by quercetin may be due, at least in part, to inhibition of tyrosine phosphorylation and PLD activation. (C) 1997 Elsevier Science Inc.
引用
收藏
页码:1503 / 1510
页数:8
相关论文
共 32 条
[1]  
BILLAH MM, 1993, CURR OPIN IMMUNOL, V5, P114
[2]   THE BIOFLAVONOID QUERCETIN INHIBITS NEUTROPHIL DEGRANULATION, SUPEROXIDE PRODUCTION, AND THE PHOSPHORYLATION OF SPECIFIC NEUTROPHIL PROTEINS [J].
BLACKBURN, WD ;
HECK, LW ;
WALLACE, RW .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1987, 144 (03) :1229-1236
[3]   CHEMOATTRACTANT SIGNALING AND LEUKOCYTE ACTIVATION [J].
BOKOCH, GM .
BLOOD, 1995, 86 (05) :1649-1660
[4]   PHOSPHOLIPASE-D ACTIVATION IS FUNCTIONALLY LINKED TO SUPEROXIDE GENERATION IN THE HUMAN NEUTROPHIL [J].
BONSER, RW ;
THOMPSON, NT ;
RANDALL, RW ;
GARLAND, LG .
BIOCHEMICAL JOURNAL, 1989, 264 (02) :617-620
[5]   ERKS - A FAMILY OF PROTEIN-SERINE THREONINE KINASES THAT ARE ACTIVATED AND TYROSINE PHOSPHORYLATED IN RESPONSE TO INSULIN AND NGF [J].
BOULTON, TG ;
NYE, SH ;
ROBBINS, DJ ;
IP, NY ;
RADZIEJEWSKA, E ;
MORGENBESSER, SD ;
DEPINHO, RA ;
PANAYOTATOS, N ;
COBB, MH ;
YANCOPOULOS, GD .
CELL, 1991, 65 (04) :663-675
[6]  
COCKCROFT S, 1994, IMMUNOPHARMACOLOGY N, P159
[7]   TYROSINE PHOSPHORYLATION AND ACTIVATION OF NADPH OXIDASE IN HUMAN NEUTROPHILS - A POSSIBLE ROLE FOR MAP KINASES AND FOR A 75 KDA PROTEIN [J].
DUSI, S ;
DONINI, M ;
ROSSI, F .
BIOCHEMICAL JOURNAL, 1994, 304 :243-250
[8]   PROTEIN-KINASE C INHIBITION BY PLANT FLAVONOIDS - KINETIC MECHANISMS AND STRUCTURE-ACTIVITY-RELATIONSHIPS [J].
FERRIOLA, PC ;
CODY, V ;
MIDDLETON, E .
BIOCHEMICAL PHARMACOLOGY, 1989, 38 (10) :1617-1624
[9]   Phospholipid signalling: Rho is only ARF the story [J].
Frohman, MA ;
Morris, AJ .
CURRENT BIOLOGY, 1996, 6 (08) :945-947
[10]   TYROSINE PHOSPHORYLATION AND OXYGEN-CONSUMPTION INDUCED BY G-PROTEINS IN NEUTROPHILS [J].
GRINSTEIN, S ;
FURUYA, W .
AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 260 (05) :C1019-C1027