Regulation of nitric oxide production by arginine metabolic enzymes
Regulation of nitric oxide production by arginine metabolic enzymes
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DOI：
10.1006/bbrc.2000.3169
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发表时间：
2000-09-07
影响因子：
3.1
通讯作者：
Gotoh, T
中科院分区：
文献类型：
--
作者：
Mori, M;Gotoh, T
一氧化氮（NO）是由一氧化氮合酶（NOS）由精氨酸合成的，而精氨酸的利用率是细胞一氧化氮生成的限速因素之一。瓜氨酸是NOS反应的副产物，可通过精氨酸琥珀酸合成酶（as）和精氨酸琥珀酸裂解酶（AL）的连续作用再循环为精氨酸，形成瓜氨酸- no循环。AS和AL可与诱导型NOS （iNOS）共诱导多种细胞类型，包括活化的巨噬细胞、血管平滑肌细胞、胶质细胞、神经元PC12细胞和胰腺β细胞。阳离子氨基酸转运蛋白(CAT)-2在活化的巨噬细胞中被诱导，而在PC12细胞中不被诱导。另一方面，精氨酸酶可以通过降低细胞内精氨酸浓度来下调NO的产生。巨噬细胞中iNOS和精氨酸酶活性受细胞因子的相互调节，这可能保证了NO的高效产生。相反，iNOS和精氨酸酶同工型（I型和II型）在脂多糖（LPS）激活的巨噬细胞中被共诱导。这些结果表明，NO的产生是由精氨酸的摄取、再循环和降解调节的。(C) 2000年学术出版社。
Nitric oxide (NO) is synthesized from arginine by NO synthase (NOS), and the availability of arginine is one of the rate-limiting factors in cellular NO production. Citrulline, which is formed as a by-product of the NOS reaction, can be recycled to arginine by successive actions of argininosuccinate synthetase (AS) and argininosuccinate lyase (AL), forming the citrulline-NO cycle. AS and sometimes AL have been shown to be coinduced with inducible NOS (iNOS) in various cell types including activated macrophages, vascular smooth muscle cells, glial cells, neuronal PC12 cells, and pancreatic beta-cells. Cationic amino acid transporter (CAT)-2 is induced in activated macrophages but not in PC12 cells. On the other hand, arginase can downregulate NO production by decreasing intracellular arginine concentrations. iNOS and arginase activities are regulated reciprocally in macrophages by cytokines, and this may guarantee the efficient production of NO. In contrast, iNOS and arginase isoforms (type I and II) are coinduced in lipopolysaccharide (LPS)-activated macrophages. These results indicate that NO production is modulated by the uptake, recycling, and degradation of arginine. (C) 2000 Academic Press.