Modulation of LDL oxidation by 7,8-dihydroneopterin |
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Authors: | Greilberger Joachim Oettl Karl Cvirn Gerhard Reibnegger Gilbert Jürgens Günther |
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Affiliation: | a Institute for Medical Chemistry and Pregl-Labratory, University of Graz, Graz, Austriab Ludwig Boltzmann Research Institute for Pediatric Thrombosis and Haemostasis, Department of Pediatrics, University of Graz, Graz, Austria |
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Abstract: | Human macrophages stimulated with interferon-γ 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. |
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Keywords: | 7 8-Dihydroneopterin Lipid hydroperoxides (LPO) Lipid peroxidation Electrophoretic mobility (EM) Free radicals Atherosclerosis |
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