Endogenous incorporation of nitric oxide from L-arginine into N-nitrosomorpholine stimulated by Escherichia coli lipopolysaccharide in the rat.
Endogenous incorporation of nitric oxide from L-arginine into N-nitrosomorpholine stimulated by Escherichia coli lipopolysaccharide in the rat.
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DOI：
10.1093/carcin/12.3.537
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发表时间：
1991-03
期刊：
影响因子：
4.7
通讯作者：
C. Leaf;J. Wishnok;S. Tannenbaum
中科院分区：
文献类型：
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作者：
C. Leaf;J. Wishnok;S. Tannenbaum
大鼠、小鼠和人类体内硝酸盐的内源性形成是通过涉及精氨酸胍基氧化的细胞过程发生的。这些过程从精氨酸到一氧化氮，随后转化为能够形成致癌亚硝胺的亲电子亚硝化剂。我们现在已经证明，内源性亚硝胺的形成可以通过体内细菌脂多糖（LPS）刺激的细胞发生。通过腹膜内注射给予大鼠吗啉的亚硝化。注射产生 N-亚硝基吗啉 (NMOR)，随后在肝脏中被氧化。 NMOR 的主要代谢物 N-亚硝基-(2-羟乙基)甘氨酸先前已被其他研究人员证明可排泄到尿液中。用 LPS、精氨酸和吗啉治疗大鼠会导致 NMOR 尿液代谢物在 24 小时内大幅增加。该过程不受同时加入大量NaNO3 的影响。因此，内源性 LPS 诱导的 NMOR 形成直接由一氧化氮在并入硝酸盐体池之前进行。纳入NMOR 的内源合成一氧化氮的比例约为3 x 10(-6)。
The endogenous formation of nitrate in the rat, mouse and human occurs through cellular processes involving the oxidation of the guanido group of arginine. These processes proceed from arginine to nitric oxide with subsequent conversion to electrophilic nitrosating agents capable of forming carcinogenic nitrosamines. We have now demonstrated that endogenous nitrosamine formation can occur via cells stimulated in vivo by bacterial lipopolysaccharide (LPS). The nitrosation of morpholine given to rats by i.p. injection yields N-nitrosomorpholine (NMOR) which is subsequently oxidized in the liver. A major metabolite of NMOR, N-nitroso-(2-hydroxyethyl)glycine, was previously shown by other investigators to be excreted into urine. Treatment of rats with LPS, arginine and morpholine creates a large increase in NMOR urinary metabolites over a 24-h period. This process is not influenced by simultaneous dosage with large amounts of NaNO3. Therefore the endogenous LPS-induced formation of NMOR proceeds directly from nitric oxide prior to incorporation into the nitrate body pool. The proportion of endogenously synthesized nitric oxide incorporated into NMOR is approximately 3 x 10(-6).