Iyamu Efemwonkiekie W, Perdew Harrison, Woods Gerald M
Division of Hematology and Oncology, Children's Mercy Hospital & Clinics, Pediatric Research Center, 2401 Gillham Road, 3730.01, Kansas City, MO 64108, USA.
Biochem Biophys Res Commun. 2008 Nov 7;376(1):116-20. doi: 10.1016/j.bbrc.2008.08.102. Epub 2008 Aug 30.
Impairment of nitric oxide bioavailability secondary to increased arginase activity and overproduction of reactive oxygen species (ROS) is thought to be a major cause of vascular complications in sickle cell disease (SCD). However, the role of ROS in the induction of arginase activity is unknown. This study investigated whether the mechanism of arginase activation involves the ROS produced during oxidative stress. Our study reveals that cysteine-iron dose-dependently stimulated arginase activity with a corresponding increase in (.)OH radical formation. The ()OH radicals produced were significantly inhibited by salicylic acid derivatives and superoxide dismutase. Surprisingly, the inhibition of (.)OH radicals parallels the inhibition of arginase activity, thus suggesting the role of cysteine-iron in the stimulation of arginase via the Fenton reaction. This is the first evidence demonstrating the participation of (.)OH radicals in the stimulation of arginase activity, and thus provides novel avenues for therapeutic modalities in hemoglobinopathies and other inflammation-mediated diseases.
一氧化氮生物利用度受损继发于精氨酸酶活性增加和活性氧（ROS）过量产生，被认为是镰状细胞病（SCD）血管并发症的主要原因。然而，ROS在诱导精氨酸酶活性中的作用尚不清楚。本研究调查了精氨酸酶激活机制是否涉及氧化应激期间产生的ROS。我们的研究表明，半胱氨酸-铁剂量依赖性地刺激精氨酸酶活性，同时（·）OH自由基形成相应增加。所产生的（·）OH自由基被水杨酸衍生物和超氧化物歧化酶显著抑制。令人惊讶的是，（·）OH自由基的抑制与精氨酸酶活性的抑制平行，因此表明半胱氨酸-铁通过芬顿反应刺激精氨酸酶的作用。这是首个证明（·）OH自由基参与刺激精氨酸酶活性的证据，从而为血红蛋白病和其他炎症介导疾病的治疗方式提供了新途径。
