The oxidation of apocynin catalyzed by myeloperoxidase: Proposal for NADPH oxidase inhibition

被引：129

作者：

Ximenes, Valdecir F. ^{[1
]}

Kanegae, Marilia P. P.

Rissato, Sandra R.

Galhiane, Mario S.

机构：

[1] Univ Estadual Paulista, Fac Ciencias, Dept Quim, Bauru, SP, Brazil

[2] Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Anal Clin, Araraquara, SP, Brazil

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2007年 / 457卷 / 02期

基金：

巴西圣保罗研究基金会;

关键词：

apocynin; myeloperoxidase; NADPH oxidase; respiratory burst; hypochlorous acid; neutrophil;

D O I：

10.1016/j.abb.2006.11.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Apocynin has been used as an efficient inhibitor of the NADPH oxidase complex and its mechanism of inhibition is linked to prior activation through the action of peroxidascs. Here we studied the oxidation of apocynin catalyzed by myeloperoxidase (MPO) and activated neutrophils. We found that apocynin is easily oxidized by MPO/H2O2 or activated neutrophils and has as products dimer and trimer derivatives. Since apocynin impedes the migration of the cytosolic component p47phox to the membrane and this effect could be related to its conjugation with essential thiol groups, we studied the reactivity of apocynin and its MPO-catalyzed oxidation products with glutathione (GSH). We found that apocynin and its oxidation products do not react with GSH. However, this thiol compound was efficiently oxidized by the apocynin radical during the MPO-catalyzed oxidation. We suggest that the reactivity of apocynin radical with thiol compounds could be involved in the inhibitory effect of this methoxy-catechol on NADPH oxidase complex. (c) 2006 Elsevier Inc. All rights reserved.

引用

页码：134 / 141

页数：8

共 25 条

[21] Effects of methoxylation of apocynin and analogs on the inhibition of reactive oxygen species production by stimulated human neutrophils [J].

Van den Worm, E ;

Beukelman, CJ ;

Van den Berg, AJJ ;

Kroes, BH ;

Labadie, RP ;

Van Dijk, H .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2001, 433 (2-3) :225-230

[22] Apocynin inhibits NADPH oxidase in phagocytes but stimulates ROS. production in non-phagocytic cells [J].

Vejrazka, M ;

Mícek, R ;

Stípek, S .

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2005, 1722 (02) :143-147

[23] Superoxide-dependent oxidation of melatonin by myeloperoxidase [J].

Ximenes, VF ;

Silva, SO ;

Rodrigues, MR ;

Catalani, LH ;

Maghzal, GJ ;

Kettle, AJ ;

Campa, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (46) :38160-38169

[24] Indole ring oxidation by activated leukocytes prevents the production of hypochlorous acid [J].

Ximenes, VF ;

Paino, IMM ;

de Faria-Oliveira, OMM ;

da Fonseca, LM ;

Brunetti, IL .

BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, 2005, 38 (11) :1575-1583

[25] Apocynin but not allopurinol prevents and reverses adrenocorticotropic hormone-induced hypertension in the rat [J].

Zhang, Y ;

Chan, MMK ;

Andrews, MC ;

Mori, TA ;

Croft, KD ;

McKenzie, KUS ;

Schyvens, CG ;

Whitworth, JA .

AMERICAN JOURNAL OF HYPERTENSION, 2005, 18 (07) :910-916

← 1 2 3 →