Role of oxidant injury on macrophage lipoprotein lipase (LPL) production and sensitivity to LPL.
We investigated, in the present study, the role of reactive oxygen intermediates (ROI) in the control of macrophage lipoprotein lipase (LPL) secretion. Exposure of murine macrophages to increasing concentrations of hydrogen peroxide (H2O2) resulted in enhanced basal LPL production and mRNA levels. The increase of LPL production was reduced in the presence of antioxidants. Oxidant stress also modulated the regulation of macrophage LPL production by tumor necrosis factor alpha (TNF alpha). While antioxidants accentuated the inhibition of LPL by TNF alpha, addition of H2O2 significantly attenuated TNF alpha-induced LPL inhibition. As LPL has been shown to induce macrophage TNF alpha release, the effect of reactive oxygen species on LPL-induced TNF alpha production was also examined. Simultaneous treatment of macrophages with LPL and H2O2 or pretreatment of macrophages with H2O2 prior to LPL stimulation decreased the LPL-induced TNF alpha release by macrophages to the same extent. Under these experimental conditions, LPL binding to macrophages was markedly decreased. These data indicate that ROI are effective enhancers of macrophage LPL production and modulate macrophage response to LPL. These effects may represent additional mechanisms through which oxidant stress may participate to the development of atherosclerosis.
Renier
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G
Department of Nutrition, Notre-Dame Hospital Research Center, University of Montreal, Quebec, Canada.
Desfaits
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Lambert
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Mikhail
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D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004351:Drug Resistance; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology*; D051379:Mice; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017931:DNA Primers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D008071:Lipoprotein Lipase