Effect of 7, 8-dihydroneopterin mediated CD36 down regulation and oxidant scavenging on oxidised low-density lipoprotein induced cell death in human macrophages. (June 2017)

• Record Type: Journal Article
• Authors: Shchepetkina, Anastasia A.; Hock, Barry D.; Miller, Allison; Kennedy, Martin A.; Gieseg, Steven P.
• Is Part Of: International journal of biochemistry & cell biology. Volume 87(2017)
• Page Start: 27
• Page End: 33
• Publication Date: 2017-06
• Subjects: 7KC 7-ketocholesterol -- acLDL acetylated low density lipoprotein -- DHE dihydroethidium -- HMDM human monocyte-derived macrophage -- LDL low density lipoprotein -- NOX NADPH-oxidase -- oxLDL oxidised low density lipoprotein -- PBS phosphate buffered saline -- PPAR-γ peroxisome proliferator-activated receptor gamma; CD36 -- oxLDL -- 7, 8-dihydroneopterin -- cell-death -- macrophage -- neopterin -- regulation; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2017.03.017
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: The role of CD36 in oxidised low-density lipoprotein (oxLDL) mediated cell death was examined by down regulating the receptor level with the macrophage generated antioxidant 7, 8‐dihydroneopterin. Down regulation of CD36 protein levels in human monocyte derived macrophages by 7, 8-dihydroneopterin corresponded to a decrease in CD36-mRNA. The oxidation products of 7, 8-dihydroneopterin, dihydroxanthopterin and neopterin did not significantly down regulate CD36. The CD36 down regulation resulted in a decrease in oxLDL uptake measured as 7-ketocholesterol accumulation. Though less oxLDL was taken up by the macrophages as a result of the 7, 8-dihydroneopterin induced down regulation in CD36 levels, the cytotoxicity of the oxLDL was not decreased. Addition of 7, 8-dihydroneopterin to oxLDL treated macrophages decreased the concentration of intracellular oxidants. In the presence of oxLDL, 7, 8-dihydroneopterin was oxidised to neopterin showing that the 7, 8-dihydroneopterin was scavenging intracellular oxidants generated in response to the oxLDL. The results show CD36 down regulation does not protect human macrophages form oxLDL cytotoxicity but 7, 8-dihydroneopterin intracellular oxidant scavenging is protective.