Firth Carole A, Yang Ya-Ting, Gieseg Steven P
Free Radical Biochemistry Laboratory, School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.
Free Radic Res. 2007 Jul;41(7):839-48. doi: 10.1080/10715760701416442.
In U937 and mouse myeloma cells, protein hydroperoxides are the predominant hydroperoxide formed during exposure to AAPH or gamma irradiation. In lipid-rich human monocyte-derived macrophages (HMDMs), we have found the opposite situation. Hydroperoxide measurements by the FOX assay showed the majority of hydroperoxides formed during AAPH incubation were lipid hydroperoxides. Lipid hydroperoxide formation began after a four hour lag period and was closely correlated with loss of cell viability. The macrophage pterin 7,8-dihydroneopterin has previously been shown to be a potent scavenger of peroxyl radicals, preventing oxidative damage in U937 cells, protein and lipoprotein. However, when given to HMDM cells, 7,8-dihydroneopterin failed to inhibit the AAPH-mediated cellular damage. The lack of interaction between 7,8-dihydroneopterin and AAPH peroxyl radicals suggests that they localize to separate cellular sites in HMDM cells. Our data shows that lipid peroxidation is the predominant reaction occurring in HMDMs, possibly due to the high lipid content of the cells.
在U937细胞和小鼠骨髓瘤细胞中，蛋白质氢过氧化物是暴露于2,2'-偶氮二异丁基脒二盐酸盐（AAPH）或γ射线照射期间形成的主要氢过氧化物。在富含脂质的人单核细胞衍生巨噬细胞（HMDM）中，我们发现了相反的情况。通过FOX法进行的氢过氧化物测量表明，在AAPH孵育期间形成的大多数氢过氧化物是脂质氢过氧化物。脂质氢过氧化物的形成在四小时的延迟期后开始，并且与细胞活力的丧失密切相关。巨噬细胞蝶呤7,8-二氢新蝶呤先前已被证明是一种有效的过氧自由基清除剂，可防止U937细胞、蛋白质和脂蛋白受到氧化损伤。然而，当给予HMDM细胞时，7,8-二氢新蝶呤未能抑制AAPH介导的细胞损伤。7,8-二氢新蝶呤与AAPH过氧自由基之间缺乏相互作用表明它们定位于HMDM细胞中的不同细胞部位。我们的数据表明，脂质过氧化是HMDM中发生的主要反应，这可能是由于细胞中脂质含量高所致。
