Endothelial nitric oxide production is tightly coupled to the citrulline-NO cycle
Endothelial nitric oxide production is tightly coupled to the citrulline-NO cycle
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DOI：
10.1016/j.niox.2007.07.001
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发表时间：
2007-11-01
影响因子：
3.9
通讯作者：
Solomonson, Larry P.
中科院分区：
文献类型：
--
作者：
Flam, Brenda R.;Eichler, Duane C.;Solomonson, Larry P.
一氧化氮（NO）是一种重要的血管舒张剂，在内皮型一氧化氮合酶（eNOS）的催化下，与L-精氨酸一起沿着生成。以前的研究表明，L-瓜氨酸再循环为L-精氨酸对内皮细胞中NO的产生至关重要。然而，没有直接证据表明L-瓜氨酸再循环为L-精氨酸与NO产生的耦合程度。我们假设，由于L-瓜氨酸通过瓜氨酸-NO循环再循环的效率，NO形成量将显著高于L-瓜氨酸形成量。为了验证这一假设，将内皮细胞与[C-14]-L-精氨酸一起孵育，并通过各种试剂刺激产生NO。同时测定NO和[C-14]-L-瓜氨酸形成的程度。NO生产超过明显的L-瓜氨酸形成的顺序为8比1，在基础和刺激条件下。作为进一步的支持，α-甲基-DL-天冬氨酸，一种瓜氨酸琥珀酸合成酶（AS）的抑制剂，瓜氨酸-NO循环的一个组成部分，以剂量依赖性方式抑制NO的产生。本研究的结果为L-瓜氨酸再循环通过瓜氨酸-NO循环与内皮NO产生的必要和有效耦合提供了证据。(c)2007爱思唯尔公司All rights reserved.
Nitric oxide (NO) is an important vasorelaxant produced along With L-Citrulline from L-arginine in a reaction catalyzed by endothelial nitric oxide synthase (eNOS). Previous Studies suggested that the recycling Of L-Citrulline to L-arginine is essential for NO production in endothelial cells. However, there is no direct evidence demonstrating the degree to which the recycling Of L-citrulline to L-arginine is coupled to NO production. We hypothesized that the amount of NO formed would be significantly higher than the amount of L-Citrulline formed due to the efficiency Of L-Citrulline recycling via the citrulline-NO cycle. To test this hypothesis, endothelial cells were incubated with [C-14]-L-arginine and stimulated by various agents to produce NO. The extent of NO and [C-14]-L-citrulline formation were simultaneously determined. NO production exceeded apparent L-Citrulline formation of the order of 8 to 1, under both basal and stimulated conditions. As further support, alpha-methyl-DL-aspartate, an inhibitor of argininosuccinate synthase (AS), a component of the citrulline-NO cycle, inhibited NO production in a dose-dependent manner. The results of this study provide evidence for the essential and efficient coupling Of L-citrulline recycling, via the citrulline-NO cycle, to endothelial NO production. (c) 2007 Elsevier Inc. All rights reserved.