Arginase and arginine dysregulation in asthma.
Arginase and arginine dysregulation in asthma.
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DOI：
10.1155/2011/736319
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Morris CR
中科院分区：
文献类型：
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作者：
Benson RC;Hardy KA;Morris CR
近年来，越来越多的证据表明，精氨酸酶（将 L-精氨酸转化为 L-鸟氨酸和尿素）通过 L-精氨酸代谢失调和一氧化氮 (NO) 稳态调节，在哮喘等肺部疾病的发病机制中发挥着关键作用。过敏性哮喘的特征是气道高反应性、炎症和重塑。通过底物竞争，精氨酸酶降低一氧化氮合酶 (NOS) 的 L-精氨酸生物利用度，从而限制 NO 的产生，从而影响气道张力和炎症。通过降低 L-精氨酸的生物利用度，精氨酸酶还可能有助于 NOS 的解偶联以及气道中促炎氧化剂过氧亚硝酸盐的形成。最后，精氨酸酶可能通过形成 L-鸟氨酸以及下游产生多胺和 L-脯氨酸而在慢性气道重塑的发展中发挥作用，这些多胺和 L-脯氨酸参与细胞增殖和胶原蛋白沉积过程。对精氨酸酶活性和 L-精氨酸生物利用度调节的进一步研究可能会揭示有前景的哮喘新治疗策略。
In recent years, evidence has accumulated indicating that the enzyme arginase, which converts L-arginine into L-ornithine and urea, plays a key role in the pathogenesis of pulmonary disorders such as asthma through dysregulation of L-arginine metabolism and modulation of nitric oxide (NO) homeostasis. Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Through substrate competition, arginase decreases bioavailability of L-arginine for nitric oxide synthase (NOS), thereby limiting NO production with subsequent effects on airway tone and inflammation. By decreasing L-arginine bioavailability, arginase may also contribute to the uncoupling of NOS and the formation of the proinflammatory oxidant peroxynitrite in the airways. Finally, arginase may play a role in the development of chronic airway remodeling through formation of L-ornithine with downstream production of polyamines and L-proline, which are involved in processes of cellular proliferation and collagen deposition. Further research on modulation of arginase activity and L-arginine bioavailability may reveal promising novel therapeutic strategies for asthma.