Inhibition of THP-1 cell-mediated low-density lipoprotein oxidation by the macrophage-synthesised pterin, 7,8-dihydroneopterin.
Human macrophages release the pterin, 7,8-dihydroneopterin when exposed to the immune stimulant gamma-interferon (IFN-gamma). Previous in vitro studies have shown 7,8-dihydroneopterin is a potent antioxidant, which inhibits copper- and peroxyl-radical mediated low-density lipoprotein (LDL) oxidation. Using THP-1 cells, a human derived monocyte-like cell line, we have found that low micromolar concentrations of 7,8-dihydroneopterin inhibit cell mediated oxidation of LDL, as measured by electrophoretic mobility, alpha-tocopherol loss, and lipid oxidation. Stimulation of the THP-1 cells with IFN-gamma caused a significant reduction in the cells' ability to oxidise LDL. The extracellular pterin concentration increased from 0 to 16 nM with IFN-gamma stimulation, while the intracellular concentration increased from 0.21 to 1.69 nmol/mg cell protein.
Gieseg
Steven P
SP
Free Radical Biochemistry Laboratory, Department of Zoology, University of Canterbury, Christchurch, New Zealand. s.gieseg@zool.canterbury.ac.nz
Cato
Sara
S
D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D019798:Neopterin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000494:pharmacology; D013997:Time Factors; D024502:alpha-Tocopherol / Q000378:metabolism
D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C000976:7,8-dihydroneopterin; D019798:Neopterin; D007371:Interferon-gamma; D024502:alpha-Tocopherol; D010100:Oxygen