Role of soluble epoxide hydrolase phosphatase activity in the metabolism of lysophosphatidic acids.
Role of soluble epoxide hydrolase phosphatase activity in the metabolism of lysophosphatidic acids.
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DOI：
10.1016/j.bbrc.2012.02.108
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发表时间：
2012-03-23
影响因子：
3.1
通讯作者：
Hammock BD
中科院分区：
文献类型：
--
作者：
Morisseau C;Schebb NH;Dong H;Ulu A;Aronov PA;Hammock BD
EPXH 2基因编码可溶性环氧化物水解酶（sEH），其具有两种不同的酶活性：环氧化物水解酶（Cterm-EH）和磷酸酶（Nterm-phos）。Cterm-EH参与来自花生四烯酸和其他不饱和脂肪酸的环氧化物的代谢，这些环氧化物是在血压调节、细胞生长、炎症和疼痛中起重要作用的内源性化学介质。虽然最近的研究结果表明Nterm-phos的补充生物作用，但其作用模式尚未得到充分了解。在此，我们证明溶血磷脂酸是Nterm-phos的优良底物。我们还表明，sEH磷酸酶活性代表了LPA细胞水解的重要（20-60%）部分，特别是在胞质溶胶中。sEH对LPA水解的这种可能作用可以解释先前与Nterm-phos相关的一些生物学。这些发现也强调了可能的细胞机制，这两个活动的sEH（EH和磷酸酶）可能有互补或相反的作用。
The EPXH2 gene encodes for the soluble epoxide hydrolase (sEH), which has two distinct enzyme activities: epoxide hydrolase (Cterm-EH) and phosphatase (Nterm-phos). The Cterm-EH is involved in the metabolism of epoxides from arachidonic acid and other unsaturated fatty acids, endogenous chemical mediators that play important roles in blood pressure regulation, cell growth, inflammation and pain. While recent findings suggested complementary biological roles for Nterm-phos, its mode of action is not well understood. Herein, we demonstrate that lysophosphatidic acids are excellent substrates for Nterm-phos. We also showed that sEH phosphatase activity represents a significant (20–60%) part of LPA cellular hydrolysis, especially in the cytosol. This possible role of sEH on LPA hydrolysis could explain some of the biology previously associated with the Nterm-phos. These findings also underline possible cellular mechanisms by which both activities of sEH (EH and phosphatase) may have complementary or opposite roles.