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
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
收藏
页码:311 / 318
页数:8
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