Modulation of LDL oxidation by 7,8-dihydroneopterin.
Human macrophages stimulated with interferon-gamma generate neopterin and 7,8-dihydroneopterin which interfere with reactive species involved in LDL oxidation. While neopterin was found to have pro-oxidative effects on copper-mediated LDL oxidation, the influence of 7,8-dihydroneopterin is more complex. This study provides detailed information that 7,8-dihydroneopterin reveals both pro-oxidative and anti-oxidative effects on copper mediated LDL oxidation. 7,8-dihydroneopterin inhibited the oxidation of native LDL effectively monitored by (i) formation of conjugated dienes, (ii) relative electrophoretic mobility (EM) and (iii) specific oxidized epitopes. Using minimally oxidized LDL (mi-LDL) or moderately oxidized LDL (mo-LDL) 7,8-dihydroneopterin changed its antioxidative behavior to a strongly pro-oxidative. Incubation of 7,8-dihydroneopterin with native LDL, mi-LDL or mo-LDL in the absence of copper ions showed that formation of conjugated dienes was more increased in mo-LDL than in mi-LDL while no diene formation was observed with native LDL. We suggest that 7,8-dihydroneopterin is a modulator for LDL oxidation in the presence of copper ions depending on the "oxidative status" of this lipoprotein.
Greilberger
Joachim
J
Institute for Medical Chemistry and Pregl-Labratory, University of Graz, Harrachgasse 21/2, A-8010, Graz, Austria. joachim.greilberger@kfunigraz.ac.at
Oettl
Karl
K
Cvirn
Gerhard
G
Reibnegger
Gilbert
G
Jürgens
Günther
G
D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D000939:Epitopes / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D019798:Neopterin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D004369:Pentetic Acid / Q000494:pharmacology
D002614:Chelating Agents; D000939:Epitopes; D008077:Lipoproteins, LDL; D016877:Oxidants; C000976:7,8-dihydroneopterin; D019798:Neopterin; D003300:Copper; D004369:Pentetic Acid; D004492:Edetic Acid