Traditional Chinese Medicine History and Literature, Institute for Literature and Culture of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Institute for Literature and Culture of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Int J Mol Sci. 2019 Jul 27;20(15):3683. doi: 10.3390/ijms20153683.
As a major component of cell membrane lipids, Arachidonic acid (AA), being a major component of the cell membrane lipid content, is mainly metabolized by three kinds of enzymes: cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Based on these three metabolic pathways, AA could be converted into various metabolites that trigger different inflammatory responses. In the kidney, prostaglandins (PG), thromboxane (Tx), leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) are the major metabolites generated from AA. An increased level of prostaglandins (PGs), TxA and leukotriene B4 (LTB) results in inflammatory damage to the kidney. Moreover, the LTB-leukotriene B4 receptor 1 (BLT1) axis participates in the acute kidney injury via mediating the recruitment of renal neutrophils. In addition, AA can regulate renal ion transport through 19-hydroxystilbenetetraenoic acid (19-HETE) and 20-HETE, both of which are produced by cytochrome P450 monooxygenase. Epoxyeicosatrienoic acids (EETs) generated by the CYP450 enzyme also plays a paramount role in the kidney damage during the inflammation process. For example, 14 and 15-EET mitigated ischemia/reperfusion-caused renal tubular epithelial cell damage. Many drug candidates that target the AA metabolism pathways are being developed to treat kidney inflammation. These observations support an extraordinary interest in a wide range of studies on drug interventions aiming to control AA metabolism and kidney inflammation.
作为细胞膜脂质的主要成分，花生四烯酸（AA）是细胞膜脂质含量的主要成分，主要通过三种酶代谢：环氧化酶（COX）、脂氧合酶（LOX）和细胞色素 P450（CYP450）酶。基于这三种代谢途径，AA 可以转化为引发不同炎症反应的各种代谢物。在肾脏中，前列腺素（PG）、血栓素（Tx）、白三烯（LTs）和羟二十碳四烯酸（HETEs）是 AA 生成的主要代谢物。前列腺素（PGs）、Tx 和白三烯 B4（LTB）水平升高会导致肾脏炎症损伤。此外，LTB-白三烯 B4 受体 1（BLT1）轴通过介导肾脏中性粒细胞的募集参与急性肾损伤。此外，AA 可以通过 19-羟基-二十碳四烯酸（19-HETE）和 20-羟二十碳四烯酸（20-HETE）调节肾脏离子转运，这两种物质都是由细胞色素 P450 单加氧酶产生的。CYP450 酶产生的环氧二十碳三烯酸（EETs）在炎症过程中对肾脏损伤也起着至关重要的作用。例如，14 和 15-EET 减轻了缺血/再灌注引起的肾小管上皮细胞损伤。许多针对 AA 代谢途径的药物候选物正在被开发用于治疗肾脏炎症。这些观察结果支持了对广泛的研究药物干预旨在控制 AA 代谢和肾脏炎症的极大兴趣。
