A protective role for nitric oxide in the oxidative modification of low density lipoproteins by mouse macrophages

FEBS Letters

Mao, Simon J.T.¹  Yates, Mark T.¹  McDonald, Ian¹  Ku, George¹  Lambert, Laurie E.¹  Whitten, Jeffrey P.¹  Mano, Masayuki¹ 

[1] Marion Merrell Dow Research Institute, 2110 E. Galbraith Road, Cincinnati, OH 45215, USA

关键词: Low density lipoprotein;    Oxidation;    Nitric oxide;    Macrophage;    Atherosclerosis;   

DOI  :  10.1016/0014-5793(92)81081-V

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Low density lipoproteins (LDL) oxidatively modified by macrophages have been shown to be atherogenic in ex vivo studies. We studied the potential role of nitric oxide (NO), a free radical produced by macrophages, in LDL modification. Human LDL (1 mg/ml) were incubated with mouse peritoneal macrophages in Ham's F-10 medium. The cells were then stimulated by interferon-γ and tumor necrosis factor-α to increase their production of NO from 1.3 to 12.2 μM in 24 h, as measured by nitrite. Lipid peroxidation of LDL, as measured by thiobarbituric acid-reactive materials (TBARS), was reduced in stimulated cells in a time-dependent manner. At 24 h, the decrease was about 27%. In the presence of an NO synthase inhibitor (N^o-aminophomoarginine), the generation of NO was diminished and the protection against LDL lipid peroxidation was reversed. The extent of LDL protein modification was also assessed by examining its electrophoretic mobility. It was found that macrophage NO reduced the change in LDL electromobility. These data indicate that the production of NO may inhibit the oxidative modification of LDL with cytokine-stimulated macrophages. We suggest that NO plays a protective role in limiting macrophage-induced LDL modification.

【 授权许可】

Unknown