Johns Hopkins University School of Medicine, 720 Rutland Ave Ross 1150, Baltimore, MD 21205, USA.
Mol Cell Biochem. 2011 Sep;355(1-2):83-9. doi: 10.1007/s11010-011-0841-2. Epub 2011 May 1.
Arginase constrains endothelial nitric oxide synthase activity by competing for the common substrate, L -Arginine. We have recently shown that inducible nitric oxide synthase (NOS2) S-nitrosates and activates arginase 1 (Arg1) leading to age-associated vascular dysfunction. Here, we demonstrate that a direct interaction of Arg1 with NOS2 is necessary for its S-nitrosation. The specific domain of NOS2 that mediates this interaction is identified. Disruption of this interaction in human aortic endothelial cells prevents Arg1 S-nitrosation and activation. Thus, disruption of NOS2-Arg1 interaction may represent a therapeutic strategy to attenuate age related vascular endothelial dysfunction.
精氨酸酶通过竞争共同底物 L-精氨酸来限制内皮型一氧化氮合酶的活性。我们最近表明，诱导型一氧化氮合酶（NOS2）对精氨酸酶 1（Arg1）进行 S-亚硝基化并使其激活，从而导致与年龄相关的血管功能障碍。在这里，我们证明 Arg1 与 NOS2 的直接相互作用对于其 S-亚硝基化是必需的。确定了介导这种相互作用的 NOS2 的特定结构域。在人主动脉内皮细胞中破坏这种相互作用可防止 Arg1 的 S-亚硝基化和激活。因此，破坏 NOS2-Arg1 相互作用可能代表一种治疗策略，可减轻与年龄相关的血管内皮功能障碍。
