Harris T R, Morisseau C, Walzem R L, Ma S J, Hammock B D
Department of Entomology and Cancer Research Center, University of California, Davis 95616, USA.
Poult Sci. 2006 Feb;85(2):278-87. doi: 10.1093/ps/85.2.278.
The mammalian soluble epoxide hydrolase (sEH) plays a role in the regulation of blood pressure and vascular homeostasis through its hydrolysis of the endothelial-derived messenger molecules, the epoxyeicosatrienoic acids. This study reports the cloning and expression of a sEH homolog from chicken liver. The resulting 63-kDa protein has an isoelectric point of 6.1. The recombinant enzyme displayed epoxide hydrolase activity when assayed with [3H]-trans-1,3-diphenylpropene oxide (t-DPPO), as well as trans-9,10-epoxystearate and the cis-8,9-, 11,12-, and 14,15- epoxyeicosatrienoic acids. The chicken enzyme displayed a lower kcat:Km for t-DPPO than the mammalian enzymes. The enzyme was sensitive to urea-based inhibitors developed for mammalian sEH. Such compounds could be used to study the role of chicken sEH in conditions in which endothelial-derived vasodilation is believed to be impaired, such as pulmonary hypertension syndrome.
哺乳动物可溶性环氧化物水解酶(sEH)通过水解内皮细胞衍生的信使分子——环氧二十碳三烯酸,在血压调节和血管稳态中发挥作用。本研究报道了从鸡肝脏中克隆和表达的一种sEH同源物。所得的63 kDa蛋白的等电点为6.1。用[3H]-反式-1,3-二苯基环氧丙烷(t-DPPO)以及反式-9,10-环氧硬脂酸和顺式-8,9-、11,12-以及14,15-环氧二十碳三烯酸进行测定时,重组酶表现出环氧化物水解酶活性。鸡酶对t-DPPO的催化常数与米氏常数之比低于哺乳动物酶。该酶对为哺乳动物sEH开发的基于尿素的抑制剂敏感。这类化合物可用于研究鸡sEH在诸如肺动脉高压综合征等内皮细胞衍生的血管舒张被认为受损的病症中的作用。