Arginase and pulmonary diseases.
Arginase and pulmonary diseases.
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DOI：
10.1007/s00210-008-0286-7
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发表时间：
2008-08
影响因子：
3.6
通讯作者：
Meurs, Herman
中科院分区：
文献类型：
--
作者：
Maarsingh, Harm;Pera, Tonio;Meurs, Herman
关键词：
最近的研究表明，将l-精氨酸转化为l-鸟氨酸和尿素的精氨酸酶可能在各种肺部疾病的发病机制中发挥重要作用。在哮喘、慢性阻塞性肺疾病（COPD）和囊性纤维化中，气道精氨酸酶活性的增加可能导致支气管扩张性一氧化氮（NO）的产生减少，从而导致气道阻塞和高反应性，这是由于一氧化氮与组成型（cNOS）和诱导型（iNOS） NO合成酶竞争其共同底物。此外，精氨酸酶诱导的l-精氨酸对iNOS的可用性降低，可能导致该酶合成NO和超氧阴离子，从而促进过氧亚硝酸盐的产生，而过氧亚硝酸盐具有促收缩和促炎作用。精氨酸酶合成l-鸟氨酸的增加也可能有助于这些疾病的气道重塑。l-鸟氨酸是多胺和l-脯氨酸的前体，这些代谢产物可能分别促进细胞增殖和胶原蛋白的产生。精氨酸酶活性升高也可能与其他肺纤维化疾病有关，包括特发性肺纤维化。最后，精氨酸酶活性的增加与原发性和继发性肺动脉高压有关，其作用是诱导血管舒张性一氧化氮水平的降低。针对精氨酸酶途径的药物可能在这些疾病中具有治疗潜力。
Recent studies have indicated that arginase, which converts l-arginine into l-ornithine and urea, may play an important role in the pathogenesis of various pulmonary disorders. In asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis, increased arginase activity in the airways may contribute to obstruction and hyperresponsiveness of the airways by inducing a reduction in the production of bronchodilatory nitric oxide (NO) that results from its competition with constitutive (cNOS) and inducible (iNOS) NO synthases for their common substrate. In addition, reduced l-arginine availability to iNOS induced by arginase may result in the synthesis of both NO and the superoxide anion by this enzyme, thereby enhancing the production of peroxynitrite, which has procontractile and pro-inflammatory actions. Increased synthesis of l-ornithine by arginase may also contribute to airway remodelling in these diseases. l-Ornithine is a precursor of polyamines and l-proline, and these metabolic products may promote cell proliferation and collagen production, respectively. Increased arginase activity may also be involved in other fibrotic disorders of the lung, including idiopathic pulmonary fibrosis. Finally, through its action of inducing reduced levels of vasodilating NO, increased arginase activity has been associated with primary and secondary forms of pulmonary hypertension. Drugs targeting the arginase pathway could have therapeutic potential in these diseases.
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DOI：
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发表时间：
2007-06-01
影响因子：
6.4
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