| Oxidant production, oxLDL uptake, and CD36 levels in human monocyte–derived macrophages are downregulated by the macrophage-generated antioxidant 7,8-dihydroneopterin. | |
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MedLine Citation:
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PMID: 20408759 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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The severity of atheroma burden in patients strongly correlates to increasing levels of plasma neopterin, the oxidation product of 7,8-dihydroneopterin. Interferon-γ stimulation of macrophages causes the synthesis of 7,8-dihydroneopterin, a potent antioxidant that inhibits oxidative damage to cells, and the cytotoxicity of oxidized low-density lipoprotein (oxLDL) to monocyte-like U937 cells but not THP-1 cells. With human monocyte-derived macrophages (HMDMs), oxLDL triggered a large oxidative stress, causing the rapid loss of cellular glutathione, glyceradehyde-3-phosphate dehydrogenase (GAPDH) inhibition, and eventual loss of viability without caspase-3 activation. Inhibition of oxLDL cytotoxicity to HMDMs occurred at 7,8-dihydroneopterin concentrations >100 μM. The oxLDL-mediated glutathione loss and GAPDH inactivation was inhibited by 7,8-dihydroneopterin. 7,8-Dihydroneopterin rapidly entered the HMDMs, suggesting that much of the protective effect was scavenging of intracellular oxidants generated in response to oxLDL. OxLDL uptake by HMDMs was reduced by 30% by 7,8-dihydroneopterin. Immunoblot analysis suggests that this decrease in oxLDL uptake was due to a significant downregulation in the levels of CD36. These results imply that 7,8-dihydroneopterin protects human macrophages both by scavenging oxidants generated in response to oxLDL and by decreasing CD36-mediated uptake of oxLDL. |
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Authors:
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Steven P Gieseg; Zunika Amit; Ya-Ting Yang; Anastasia Shchepetkina; Hanadi Katouah |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Antioxidants & redox signaling Volume: 13 ISSN: 1557-7716 ISO Abbreviation: Antioxid. Redox Signal. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-07 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100888899 Medline TA: Antioxid Redox Signal Country: United States |
Other Details:
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Languages: eng Pagination: 1525-34 Citation Subset: IM |
Affiliation:
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Free Radical Biochemistry Laboratory, School of Biological Sciences, University of Canterbury, Christchurch, New Zealand. steven.gieseg@canterbury.ac.nz |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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