INHIBITORY EFFECT OF NEOPTERIN ON NADPH-DEPENDENT SUPEROXIDE-GENERATING OXIDASE OF RAT PERITONEAL-MACROPHAGES

被引：73

作者：

KOJIMA, S ^{[1
]}

NOMURA, T ^{[1
]}

ICHO, T ^{[1
]}

KAJIWARA, Y ^{[1
]}

KITABATAKE, K ^{[1
]}

KUBOTA, K ^{[1
]}

机构：

[1] ASAHI BREWERY CO LTD,APPL TECHNOL RES LAB,OHTA KU,TOKYO 143,JAPAN

来源：

FEBS LETTERS | 1993年 / 329卷 / 1-2期

关键词：

NEOPTERIN; ANTIOXIDANT; SUPEROXIDE; NADPH-OXIDASE;

D O I：

10.1016/0014-5793(93)80207-B

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：

The effect of the oxidized form of neopterin (NP) on the NADPH-dependent superoxide-generating oxidase (NADPH-oxidase) was investigated in both whole-cell and cell-free activation systems by using peritoneal macrophages of rats which had received an intraperitoneal injection of mineral oil. In the whole-cell system, NP remarkably inhibited the generation of superoxides in macrophages stimulated with phorbol myristate acetate (PMA). NP also showed an significant suppression of the activation of superoxide-generating NADPH-oxidase in the cell-free system using solubilized membranes and sodium dodecyl sulfate (SDS) as a stimulant. The 50%-inhibitory concentration (IC50) of NP was about 1 muM in both assay systems. In a kinetic study, competitive inhibition of the NADPH-oxidase by NP was observed in the cell-free system with a calculated inhibition constant (K(i)) of 6.50 muM. These findings suggest that NP may play an important role in the suppression of superoxide generation via the inhibition of the NADPH-oxidase in phagocytes.

引用

页码：125 / 128

页数：4

共 21 条

[1]

ABITA JP, 1985, LANCET, V2, P51

[2] DEPENDENCE ON O-2- GENERATION BY XANTHINE-OXIDASE OF PATHOGENESIS OF INFLUENZA-VIRUS INFECTION IN MICE [J].

AKAIKE, T ;

ANDO, M ;

ODI, T ;

DOI, T ;

IJIRI, S ;

ARAKI, S ;

MAEDA, H .

JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (03) :739-745

[3] SUBCELLULAR-LOCALIZATION OF THE B-CYTOCHROME COMPONENT OF THE HUMAN NEUTROPHIL MICROBICIDAL OXIDASE - TRANSLOCATION DURING ACTIVATION [J].

BORREGAARD, N ;

HEIPLE, JM ;

SIMONS, ER ;

CLARK, RA .

JOURNAL OF CELL BIOLOGY, 1983, 97 (01) :52-61

[4]

CURNUTTE JT, 1987, J BIOL CHEM, V262, P6450

[5] IMMUNE-RESPONSE ASSOCIATED PRODUCTION OF NEOPTERIN - RELEASE FROM MACROPHAGES PRIMARILY UNDER CONTROL OF INTERFERON-GAMMA [J].

HUBER, C ;

BATCHELOR, JR ;

FUCHS, D ;

HAUSEN, A ;

LANG, A ;

NIEDERWIESER, D ;

REIBNEGGER, G ;

SWETLY, P ;

TROPPMAIR, J ;

WACHTER, H .

JOURNAL OF EXPERIMENTAL MEDICINE, 1984, 160 (01) :310-316

[6]

HUBER C, 1983, J IMMUNOL, V130, P1047

[7] PROTECTIVE EFFECTS OF TETRAHYDRONEOPTERIN AGAINST FREE RADICAL-INDUCED INJURY [J].

ICHO, T ;

KOJIMA, S ;

SHINOHARA, N ;

KAJIWARA, Y ;

KITABATAKE, K ;

KUBOTA, K .

BIOCHEMICAL PHARMACOLOGY, 1993, 45 (10) :1953-1958

[8] NEOPTERIN AS AN ENDOGENOUS ANTIOXIDANT [J].

KOJIMA, S ;

ICHO, T ;

KAJIWARA, Y ;

KUBOTA, K .

FEBS LETTERS, 1992, 304 (2-3) :163-166

[9]

KOJIMA S, 1993, IN PRESS J PHARM EXP

[10]

LOWRY OH, 1951, J BIOL CHEM, V193, P265

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