Disease relevance of Ephx2

• Using antibodies against rat liver cEH, 24 positive clones were picked upon colony blot screening of a pEX 1/E. coli POP 2136 expression library.(ABSTRACT TRUNCATED AT 250 WORDS)[1]
• Lipopolysaccharide-induced mortality, systemic hypotension, and histologically evaluated tissue injury were substantially diminished by administration of urea-based, small-molecule inhibitors of sEH to C57BL/6 mice [2].
• Mammary gland transfer RNA's (tRNA'S) of CEH mice infected with mammary tumor virus were analyzed in the preneoplastic state and compared to tRNAs of virus-free C3Hf mice and another uninfected strain, C57BL/6, which is completely resistant to cancer [3].
• In order to investigate the involvement of amino acids in the catalytic mechanism of the soluble epoxide hydrolase, different mutants of the murine enzyme were produced using the baculovirus expression system [4].
• The temperature effect on the testicular CEH was demonstrated in vivo by assaying the enzyme following unilateral cryptorchidism [5].

High impact information on Ephx2

• In the presence of adamantyl-ureido-dodecanoic acid (AUDA), a soluble epoxide hydrolase (sEH)-specific inhibitor, EETs increased PPARgamma transcription activity in endothelial cells and 3T3-L1 preadipocytes [6].
• Rapid purification of cytosolic epoxide hydrolase from normal and clofibrate-treated animals by affinity chromatography [7].
• The increases of quinone reductase activities in liver and digestive tissues in response to BHA were comparable to the increases previously observed in glutathione S-transferase (EC 2.5.1.18) and epoxide hydratase (EC 3.3.2.3) activities [8].
• Western blotting of subcellular fractions obtained from isolated rat hepatocytes revealed that the immunoreactive 106-kd CEH was exclusively localized in microsomes [9].
• We have recently purified a cholesteryl ester hydrolase (CEH) from rat liver microsomes [9].

Biological context of Ephx2

• By comparing the cDNA sequence of this newly identified variant of soluble epoxide hydrolase (referred to as Ephx2B) with the mouse genome database, an exon was identified that corresponds to its unique 5' cDNA sequence [10].
• Targeted disruption of soluble epoxide hydrolase reveals a role in blood pressure regulation [11].
• Corroboratory data are presented to show that the Eph-1 locus on chromosome 1 is the site of at least one microsomal epoxide hydratase gene [12].
• A clofibrate-induced mouse liver cDNA library was prepared and used to isolate the coding sequence for soluble epoxide hydrolase [13].
• Translation of the resulting 1659-bp open reading frame produced a 553-residue protein (62,527 Da) containing deduced peptide segments that matched the amino acid sequences of six peptide fragments isolated previously from CNBr digests of pure murine soluble epoxide hydrolase [13].

Anatomical context of Ephx2

• An increase in cytosolic epoxide hydrolase (cEH) activity occurs in the livers of mice treated with peroxisome proliferating-hypolipidemic-nongenotoxic carcinogens [14].
• Expression of the composite cDNA in COS-7 cells resulted in a 5-10-fold increase in soluble epoxide hydrolase activity and a similar increase in soluble epoxide hydrolase protein amount compared to mock-transfected or vector control-transfected cells [13].
• The anti-mouse liver cytosolic epoxide hydrolase antibody was found to precipitate the whole trans-stilbene oxide hydrolase activity also from liver cytosol of nafenopin-treated mice, which indicates the presence of a single cytosolic epoxide hydrolase following induction [15].
• Clofibrate treatment was found to increase total protein synthesis, synthesis of soluble epoxide hydrolase and translational efficiency of the isolated polyribosomes [16].
• The in vitro translation products were investigated in a rabbit reticulocyte cell-free system by immunoprecipitation of cytosolic epoxide hydrolase, catalase and albumin [16].

Associations of Ephx2 with chemical compounds

• Properties of cytosolic epoxide hydrolase purified from the liver of untreated and clofibrate-treated mice. Purification procedure and physiochemical characterization of the pure enzymes [17].
• PB, BNF, and BHA produced the expected effects on mEH, cEH, and cGST in rat and mouse livers, whereas the testes were generally nonresponsive to the inducers [18].
• To examine this possibility, blood pressure and renal arachidonic acid metabolism were examined in mice with a targeted disruption of the soluble epoxide hydrolase gene [11].
• Catalase and cytosolic epoxide hydrolase activities are inhibited by hydroxylated metabolites of 2-amino-4,5-diphenylthiazole (DPT) [19].
• Other compounds that inhibit both catalase and cytosolic epoxide hydrolase activities, but do not inhibit microsomal epoxide hydrolase activity, are nordihydroguaiaretic acid and 2-aminothiazole [19].

Regulatory relationships of Ephx2

• Selective inhibition of cytosolic epoxide hydrolase activity in vitro by compounds that inhibit catalase [19].
• Soluble epoxide hydrolase is a main effector of angiotensin II-induced hypertension [20].

Other interactions of Ephx2

• Both the increase of cEH activity and the appearance of mEH-like activity in the cytosol are novel responses of epoxide metabolizing enzymes, which may be related to the novel cellular responses that follow clofibrate treatment, peroxisome proliferation, hypolipidemia, and nongenotoxic carcinogenesis [14].
• SSLP markers were then used to confirm the location of soluble epoxide hydrolase at 14.0 +/- 3.7 cM distal to Np-1 and 19.2 +/- 4.3 cM proximal to D14Mit7 [21].
• Renal microsomal cytochrome P-450 monooxygenase-dependent metabolism of arachidonic acid generates a series of regioisomeric epoxyeicosatrienoic acids that can be further metabolized by soluble epoxide hydrolase to the corresponding dihydroxyeicosatrienoic acids [11].
• Systolic blood pressure of male soluble epoxide hydrolase-null mice was lower compared with wild-type mice in both the absence and presence of dietary salt loading [11].
• These data provide the first direct evidence for a role for soluble epoxide hydrolase in blood pressure regulation and identify this enzyme as a novel and attractive target for therapeutic intervention in hypertension [11].

Analytical, diagnostic and therapeutic context of Ephx2

• Furthermore, Ouchterlony immunodiffusion using antibodies raised in rabbits towards the control form of cytosolic epoxide hydrolase revealed identity between the two forms of cytosolic epoxide hydrolase, but no reaction with the microsomal epoxide hydrolase was observed [17].
• Molecular cloning and expression of murine liver soluble epoxide hydrolase [13].
• Enzyme assays and immunoblotting results suggest significant quantitative differences in expression of soluble epoxide hydrolase among three mouse strains [21].
• In situ hybridization to mouse metaphase chromosomes using a soluble epoxide hydrolase cDNA probe showed that soluble epoxide hydrolase maps at band D of chromosome 14 [21].
• Northern blotting analysis showed that soluble epoxide hydrolase mRNA levels were correlated with the relative level of soluble epoxide hydrolase enzyme activity and soluble epoxide hydrolase protein in all three mouse strains [21].

References