Protection of U937 cells from free radical damage by the macrophage synthesized antioxidant 7,8-dihydroneopterin

被引：37

作者：

Gieseg, SP ^{[1
]}

Whybrow, J ^{[1
]}

Glubb, D ^{[1
]}

Rait, C ^{[1
]}

机构：

[1] Univ Canterbury, Dept Zool, Free Rad Biochem Lab, Christchurch 1, New Zealand

来源：

FREE RADICAL RESEARCH | 2001年 / 35卷 / 03期

关键词：

neopterin; macrophage; antioxidant; free-radical; peroxidation; hypochlorite;

D O I：

10.1080/10715760100300841

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：

Interferon-gamma stimulation of human macrophages causes the synthesis and release of neopterin and its reduced form 7,8-dihydroneopterin (7,8-NP). The purpose of this cellular response is undetermined but in vitro experiments suggests 7,8-NP is an antioxidant. We have found 7,8-NP can protect monocyte-like U937 cells from oxidative damage. 7,8-NP inhibited ferrous ion and hypochlorite mediated loss of cell viability. Fe++ mediated lipid peroxidation was effectively inhibited by 7,8-NP, however no correlation was found between peroxide concentration and cell viability. Hypochlorite was scavenged by 7,8-NP, preventing the loss of cell viability. 7,8-NP was less effective in inhibiting H2O2-mediated loss of cell viability with significant inhibition only occurring at high 7,8-NP concentrations. Analysis of cellular protein hydrolysates showed none of the oxidants caused the formation of any protein bound DOPA or dityrosine but did show 7,8-NP prevented the loss of cellular tyrosine by HOCL Our data suggests macrophages may synthesize 7,8-NP for antioxidant protection during inflammatory events in vivo.

引用

页码：311 / 318

页数：8

共 25 条

[1]

[Anonymous], 1992, NEOPTERIN BIOCH METH

[2]

DEAN RT, 1996, FREE RADICALS PRACTI, P171

[3] A COMPARATIVE-EVALUATION OF THIOBARBITURIC ACID METHODS FOR THE DETERMINATION OF MALONDIALDEHYDE IN BIOLOGICAL-MATERIALS [J].

DRAPER, HH ;

SQUIRES, EJ ;

MAHMOODI, H ;

WU, J ;

AGARWAL, S ;

HADLEY, M .

FREE RADICAL BIOLOGY AND MEDICINE, 1993, 15 (04) :353-363

[4] IRON INDUCES LIPID-PEROXIDATION IN CULTURED MACROPHAGES, INCREASES THEIR ABILITY TO OXIDATIVELY MODIFY LDL, AND AFFECTS THEIR SECRETORY PROPERTIES [J].

FUHRMAN, B ;

OIKNINE, J ;

AVIRAM, M .

ATHEROSCLEROSIS, 1994, 111 (01) :65-78

[5] 7,8-DIHYDRONEOPTERIN INHIBITS LOW-DENSITY-LIPOPROTEIN OXIDATION IN-VITRO - EVIDENCE THAT THIS MACROPHAGE SECRETED PTERIDINE IS AN ANTIOXIDANT [J].

GIESEG, SP ;

REIBNEGGER, G ;

WACHTER, H ;

ESTERBAUER, H .

FREE RADICAL RESEARCH, 1995, 23 (02) :123-136

[6] PROTEIN-BOUND 3,4-DIHYDROXYPHENYLALANINE IS A MAJOR REDUCTANT FORMED DURING HYDROXYL RADICAL DAMAGE TO PROTEINS [J].

GIESEG, SP ;

SIMPSON, JA ;

CHARLTON, TS ;

DUNCAN, MW ;

DEAN, RT .

BIOCHEMISTRY, 1993, 32 (18) :4780-4786

[7] Inhibition of haemolysis by the macrophage synthesized antioxidant, 7,8-dihydroneopterin [J].

Gieseg, SP ;

Maghzal, G ;

Glubb, D .

REDOX REPORT, 2000, 5 (2-3) :98-100

[8]

GIESEG SP, 2001, IN PRESS FREE RADICA

[9]

GIULIVI C, 1994, METHOD ENZYMOL, V233, P363

[10] p-hydroxyphenylacetaldehyde is the major product of L-tyrosine oxidation by activated human phagocytes - A chloride-dependent mechanism for the conversion of free amino acids into reactive aldehydes by myeloperoxidase [J].

Hazen, SL ;

Hsu, FF ;

Heinecke, JW .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (04) :1861-1867

← 1 2 3 →