15-lipoxygenase-1 in the vasculature: expanding roles in angiogenesis.
15-lipoxygenase-1 in the vasculature: expanding roles in angiogenesis.
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DOI：
10.1161/circresaha.107.170191
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发表时间：
2008-02
影响因子：
20.1
通讯作者：
N. Mochizuki;Young-Guen Kwon
中科院分区：
文献类型：
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作者：
N. Mochizuki;Young-Guen Kwon
参见相关文章，第177-184页，脂氧合酶（LO）构成催化多不饱和脂肪酸立体选择性二氧化成其相应的氢过氧衍生物的酶的异质家族。1，2在哺乳动物中，LO根据其花生四烯酸氧化的位置特异性分为5-、8-、1,2-、和15-LO。1 -3这些酶在多种生理和病理过程中诱导细胞的结构和代谢变化，例如分化、致癌、炎症和动脉粥样硬化形成。越来越多的研究表明，各种LO途径在人类疾病（特别是癌症和动脉粥样硬化）的发病机制中具有不同且相反的作用。2 -5与多种LO亚型的存在一致，在各种细胞类型中发现了多种花生四烯酸的中间产物和终产物，它们反过来激活不同的信号级联，导致不同的结果。因此，对靶细胞中单个同工酶的表达模式和相应代谢物的生物学作用的复杂理解应该是预测其在疾病过程中的作用的先决条件。在4个哺乳动物LO亚家族中，15-脂氧合酶-1（在小鼠中也称为12/15-脂氧合酶）催化游离花生四烯酸转化为12-氢过氧-二十碳四烯酸和15-氢过氧-二十碳四烯酸以及亚油酸转化为13-氢过氧-十八碳二烯酸（13-HPODE）（还原产物为13-HODE）。3，4人15-LO-1和小鼠12/15-LO酶也代谢更复杂的脂质，包括磷脂、胆固醇酯和血浆脂蛋白。15-LO-1最初被认为是可与线粒体膜脂质反应的网织红细胞LO，6但随后，在各种类型的细胞中报道了15-LO-1的组成型表达，例如未成熟红细胞、嗜酸性粒细胞和气道上皮细胞。3此外，在血管细胞中检测到12/15-LO的类花生酸产物，和15-LO-1蛋白已被证明定位于兔的主动脉粥样硬化病变.
See related article, pages 177–184 Lipoxygenases (LOs) constitute a heterogeneous family of enzymes that catalyze the stereoselective dioxygenation of polyunsaturated fatty acids to their corresponding hydroperoxy derivatives.1,2 In mammals, LOs are categorized with respect to their positional specificity of arachidonic acid oxygenation into 5-, 8-, 12-, and 15-LOs.1–3 These enzymes induce structural and metabolic changes in cells during a wide variety of physiological and pathological processes, such as differentiation, carcinogenesis, inflammation, and atherogenesis. Accumulating studies have suggested diverse and opposing roles for the various LO pathways in the pathogenesis of human diseases, particularly cancer and atherosclerosis.2–5 Consistent with the existence of multiple isoforms of LOs, a variety of intermediate and end products of arachidonic acids are found in various cell types, and they in turn activate diverse signaling cascades, resulting in diverse outcomes. Therefore, sophisticated understanding of the expression pattern of individual isozymes in the target cells and biological actions of the corresponding metabolites should be prerequisite for predicting their roles in disease processes. Among the 4 mammalian LO subfamilies, 15-lipoxygenase-1 (also known as 12/15-lipoxygenase in mice) catalyzes the transformation of free arachidonic acid to 12-hydroperoxy-eicosatetraenoic acid and15-hydroperoxyeicosatetraenoic acid and the transformation of linoleic acid to 13-hydroperoxyoctadecadienoic acid (13-HPODE) (the reduced product is 13-HODE).3,4 Both human 15-LO-1 and mouse 12/15-LO enzymes also metabolize more complex lipids, including phospholipids, cholesterol esters, and plasma lipoproteins. 15-LO-1 was considered initially to be the reticulocyte LO that can react with mitochondrial membrane lipids,6 but subsequently, a constitutive expression of 15-LO-1 has been reported in various types of cells, such as immature red blood cells, eosinophils, and airway epithelial cells.3 In addition, the eicosanoid products of 12/15-LO have been detected in vascular cells, and 15-LO-1 protein has been shown to be localized to aortic atherosclerotic lesions in rabbits …