Gieseg S P, Whybrow J, Glubb D, Rait C
Free Radical Biochemistry Laboratory, Department of Zoology, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.
Free Radic Res. 2001 Sep;35(3):311-8. doi: 10.1080/10715760100300841.
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.
γ-干扰素刺激人类巨噬细胞会导致新蝶呤及其还原形式7,8-二氢新蝶呤（7,8-NP）的合成与释放。这种细胞反应的目的尚不确定，但体外实验表明7,8-NP是一种抗氧化剂。我们发现7,8-NP可以保护单核细胞样U937细胞免受氧化损伤。7,8-NP抑制亚铁离子和次氯酸盐介导的细胞活力丧失。7,8-NP有效抑制了Fe++介导的脂质过氧化，然而，过氧化物浓度与细胞活力之间未发现相关性。7,8-NP清除了次氯酸盐，防止细胞活力丧失。7,8-NP在抑制过氧化氢介导的细胞活力丧失方面效果较差，只有在高浓度的7,8-NP时才会出现显著抑制。对细胞蛋白水解产物的分析表明，没有一种氧化剂会导致形成任何与蛋白质结合的多巴或二酪氨酸，但确实表明7,8-NP可防止次氯酸导致细胞酪氨酸的损失。我们的数据表明，巨噬细胞可能在体内炎症事件期间合成7,8-NP以进行抗氧化保护。
