Effects of nitric oxide on cholesterol metabolism in macrophages.
Nitric oxide (NO) is associated with atherogenic process by inhibiting the proliferation of vascular smooth muscle cells, adhesion of monocyte/macrophages, aggregation and adhesion of platelets and oxidation of LDL, but it is not clear whether NO affects cellular cholesterol metabolism or not. We investigated cholesterol metabolism in murine macrophages (J774A.1) by regulating NO production. Incubation with S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, had no influence on cellular cholesterol accumulation induced by LDL or acetylated LDL (acetyl-LDL). Lipopolysaccharide (LPS) stimulated NO production in a dose-dependent manner in the presence of LDL or acetyl-LDL but did not change LDL-induced cellular cholesterol accumulation. In the presence of acetyl-LDL, LPS stimulated NO production but significantly inhibited cholesteryl ester accumulation in a dose-dependent manner (37.7% decrease by 100 micrograms/ml of LPS), but LPS simulation did not change free cholesterol content. NG-monomethyl-L-arginine (L-NMMA), inhibitor of NO synthase, suppressed NO production and addition of L-arginine restored NO production, but these regulations did not alter LPS-induced esterified cholesterol reduction. These results suggest that NO generation in atherosclerotic lesions does not influence cholesterol metabolism in macrophages.
Shimizu
H
H
First Department of Internal Medicine, Kobe University, School of Medicine, Japan.
Taniguchi
T
T
Ishikawa
Y
Y
Yokoyama
M
M
D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; C032629:acetyl-LDL; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D010396:Penicillamine