The importance of the lipoxygenase-hepoxilin pathway in the mammalian epidermal barrier.
The importance of the lipoxygenase-hepoxilin pathway in the mammalian epidermal barrier.
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DOI：
10.1016/j.bbalip.2013.08.020
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发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Brash AR
中科院分区：
文献类型：
--
作者：
Muñoz-Garcia A;Thomas CP;Keeney DS;Zheng Y;Brash AR
本文综述了参与表皮屏障功能的两种关键脂氧合酶（LOX）的发现背景，12 R-LOX和eLOX 3，以及我们目前对它们功能的看法。在外表皮中，它们的连续作用将ω-羟基神经酰胺中酯化的亚油酸氧化为肝氧素相关衍生物。简要回顾了海泊西林和三羟西林生物化学的相关背景。我们概述的证据表明，亚油酸的神经酰胺是天然底物的两个LOX酶和我们的建议，其重要性在建设表皮水屏障。我们的假设是，氧化促进水解的氧化亚油酸酯部分从神经酰胺。ω-羟基神经酰胺产生的游离ω-羟基与角质细胞表面上的蛋白质共价结合，形成角质细胞脂质包膜，这是一种关键的屏障组分。了解LOX酶及其肝素产物的作用，应提供合理的方法来改善治疗的先天性鱼鳞病涉及受损的屏障功能。
This review covers the background to discovery of the two key lipoxygenases (LOX) involved in epidermal barrier function, 12R-LOX and eLOX3, and our current views on their functioning. In the outer epidermis, their consecutive actions oxidize linoleic acid esterified in ω-hydroxy-ceramide to a hepoxilin-related derivative. The relevant background to hepoxilin and trioxilin biochemistry is briefly reviewed. We outline the evidence that linoleate in the ceramide is the natural substrate of the two LOX enzymes and our proposal for its importance in construction of the epidermal water barrier. Our hypothesis is that the oxidation promotes hydrolysis of the oxidized linoleate moiety from the ceramide. The resulting free ω-hydroxyl of the ω-hydroxyceramide is covalently bound to proteins on the surface of the corneocytes to form the corneocyte lipid envelope, a key barrier component. Understanding the role of the LOX enzymes and their hepoxilin products should provide rational approaches to ameliorative therapy for a number of the congenital ichthyoses involving compromised barrier function.
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影响因子：
6.5
作者：
Cronin, Annette;Decker, Martina;Arand, Michael
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影响因子：
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DOI：
10.1073/pnas.95.12.6744
发表时间：
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影响因子：
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作者：
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