Nitrosation by stimulated macrophages. Inhibitors, enhancers and substrates.

Nitrosation by stimulated macrophages. Inhibitors, enhancers and substrates.
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受刺激的巨噬细胞进行亚硝化。

DOI:
10.1093/carcin/10.3.563
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发表时间:
1989
期刊:
影响因子:
4.7
通讯作者:
Tannenbaum,SR
Tannenbaum,SR
中科院分区:
医学2区
文献类型:
--
作者:
Kosaka,H;Wishnok,JS;Miwa,M;Leaf,CD;Tannenbaum,SR

文献摘要

被引文献

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大环内酯及其永生化细胞系可通过精氨酸的氧化活化形成亚硝酸盐和硝酸盐,并伴随着N-亚硝基化合物的形成。通过使用已知抑制或增强酸催化亚硝化作用的化合物,研究了亚硝胺形成的机理。氮受体的范围已经扩大到包括脲以及不同pKa和结构的胺。结果与NO被氧化为N2 O3和N2 O 4的机理一致,N2 O3和N2 O 4能够使胺亚硝化,但不能使脲或酰胺亚硝化,这与最近观察到的巨噬细胞无细胞提取物可以将精氨酸氧化为NO相一致。抗坏血酸对完整活化的巨噬细胞的作用是复杂的,因为亚硝酸盐的形成在很宽的抗坏血酸浓度范围内增强(5-500 μM),而亚硝化作用在抗坏血酸浓度>50 μM时受到抑制。
Macrophages and their immortalized cell lines can be activated to form nitrite and nitrate via oxidation of arginine and this is accompanied by the formation ofN-nitroso compounds. The mechanism of nitrosamine formation has been investigated through the use of compounds which are known either to inhibit or enhance acid-catalyzed nitrosation. The range of nitrogen acceptors has been expanded to include ureas as well as amines of varying pKaand structure. The results are consistent with a mechanism in which NO is oxidized to N2O3and N2O4, which are capable of nitrosating amines, but not ureas or amides, at neutral pH. This is in agreement with a recent observation that macrophage cell-free extracts can oxidize arginine to NO. The effect of ascorbic acid on intact activated macrophages is complex since nitrite formation is enhanced over a very wide range of ascorbate concentrations (5–500 μM) while nitrosation is inhibited at ascorbate concentrations >50 μM.