Sura Priyanka, Sura Radhakrishna, Enayetallah Ahmed E, Grant David F
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, USA.
J Histochem Cytochem. 2008 Jun;56(6):551-9. doi: 10.1369/jhc.2008.950659. Epub 2008 Mar 3.
Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid, which function in the brain to regulate cerebral blood flow and protect against ischemic brain injury. EETs are converted by soluble epoxide hydrolase (sEH) to the corresponding inactive diol metabolites. Previous animal studies have indicated that sEH gene deletion or treatment with sEH inhibitors results in increased levels of EETs and protection against stroke-induced brain damage. To begin elucidating the underlying mechanism for these effects, we sought to determine the distribution, expression, and activity of sEH in human brain samples obtained from patients with no neurological changes/pathologies. Immunohistochemical analyses showed the distribution of sEH mainly in the neuronal cell bodies, oligodendrocytes, and scattered astrocytes. Surprisingly, in the choroid plexus, sEH was found to be highly expressed in ependymal cells. Vascular localization of sEH was evident in several regions, where it was highly expressed in the smooth muscles of the arterioles. Western blot analysis and enzyme assays confirmed the presence of sEH in the normal brain. Our results indicate differential localization of sEH in the human brain, thus suggestive of an essential role for this enzyme in the central nervous system. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.
环氧二十碳三烯酸（EETs）是花生四烯酸的细胞色素P450代谢产物，在大脑中发挥调节脑血流量和预防缺血性脑损伤的作用。EETs可被可溶性环氧化物水解酶（sEH）转化为相应的无活性二醇代谢产物。以往的动物研究表明，sEH基因缺失或用sEH抑制剂治疗会导致EETs水平升高，并预防中风引起的脑损伤。为了开始阐明这些作用的潜在机制，我们试图确定从无神经变化/病变的患者获取的人脑样本中sEH的分布、表达和活性。免疫组织化学分析显示sEH主要分布在神经元细胞体、少突胶质细胞和散在的星形胶质细胞中。令人惊讶的是，在脉络丛中，发现sEH在室管膜细胞中高度表达。sEH在几个区域的血管定位很明显，在小动脉平滑肌中高度表达。蛋白质印迹分析和酶活性测定证实了正常大脑中存在sEH。我们的结果表明sEH在人脑中的定位存在差异，因此提示该酶在中枢神经系统中具有重要作用。本文包含在线补充材料，网址为http://www.jhc.org。请在线访问本文以查看这些材料。
