Lipid oxidation predominates over protein hydroperoxide formation in human monocyte-derived macrophages exposed to aqueous peroxyl radicals.
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.
Firth
Carole A
CA
Free Radical Biochemistry Laboratory, School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.
Yang
Ya-Ting
YT
Gieseg
Steven P
SP
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009101:Multiple Myeloma; D010545:Peroxides / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D000578:Amidines; D010545:Peroxides; D011506:Proteins; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; C049375:perhydroxyl radical; C046728:2,2'-azobis(2-amidinopropane); D006861:Hydrogen Peroxide