5-Lipoxygenase is not essential in macrophage-mediated oxidation of low-density lipoprotein.
The concentration-dependent effects of a series of lipoxygenase inhibitors and antioxidants on the macrophage-mediated oxidative modification of low-density lipoprotein (LDL) were measured. Their influence on macrophage 5-lipoxygenase pathway activity was also studied over the same concentration range. No correlation between inhibition of 5-lipoxygenase and of macrophage-mediated oxidation of LDL was observed. The capacity of the compounds to prevent cell-mediated modification of LDL could be explained in terms of their activity as either aqueous- or lipid-peroxyl radical scavengers. Two potent 5-lipoxygenase inhibitors (MK 886 and Revlon 5901), which had no radical-scavenging properties, were unable to block LDL modification. It is concluded that 5-lipoxygenase is not essential for LDL oxidation by macrophages.
Jessup
W
W
Heart Research Institute, Camperdown, Sydney, N.S.W. Australia.
Darley-Usmar
V
V
O'Leary
V
V
Bedwell
S
S
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D044482:Benzeneacetamides; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects; D016166:Free Radical Scavengers; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000378:metabolism*; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D010084:Oxidation-Reduction; D002722:Chlorobenzenes
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015117:5,8,11,14-Eicosatetraynoic Acid; D000975:Antioxidants; D001094:Arachidonate 5-Lipoxygenase; D044482:Benzeneacetamides; D002084:Butylated Hydroxytoluene; D016166:Free Radical Scavengers; D006877:Hydroxamic Acids; D007211:Indoles; D008077:Lipoproteins, LDL; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol; C060893:MK-886; D002722:Chlorobenzenes; C056614:N-(3-phenoxycinnamyl)acetohydroxamic acid