Epoxide hydrolase activity in isolated peroxisomes of mouse liver

Waechter, F.; Bentley, Philip; Bieri, F.; Stäubli, W.; Völkl, Alfred; Fahimi, H. Dariush

doi:10.1016/0014-5793(83)80583-3

Cited by 54 publications

(11 citation statements)

References 14 publications

(3 reference statements)

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“…Although sEH is primarily localized in cytosol [50] its presence in mitochondria has been controversial. Initially sEH was thought to be localized to mitochondria as well as cytosol, but it was subsequently assigned to peroxisomes in addition to cytosol [35,36,51,52]. Our results indicate that the majority of the sEH in liver of the CE, as in other species, is in cytosol (about 75%; data not shown).…”

Section: Discussionmentioning

confidence: 54%

Mitochondrial P450-dependent arachidonic acid metabolism by TCDD-induced hepatic CYP1A5; conversion of EETs to DHETs by mitochondrial soluble epoxide hydrolase

Labitzke¹,

Diani-Moore²,

Rifkind³

2007

Archives of Biochemistry and Biophysics

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Several P450 enzymes localized in the endoplasmic reticulum and thought to be involved primarily in xenobiotic metabolism, including mouse and rat CYP1A1 and mouse CYP1A2, have also been found to translocate to mitochondria. We report here that the environmental toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces enzymatically active CYP1A4/1A5, the avian orthologs of mammalian CYP1A1/1A2, in chick embryo liver mitochondria as well as in microsomes. P450 proteins and activity levels (CYP1A4-dependent 7-ethoxyresorufin-O-deethylase and CYP1A5-dependent arachidonic acid epoxygenation) in mitochondria were 23-40% of those in microsomes. DHET formation by mitochondria was twice that of microsomes and was attributable to a mitochondrial soluble epoxide hydrolase as confirmed by Western blotting with antiEPHX2, conversion by mitochondria of pure 11,12 and 14,15-EET to the corresponding DHETs and inhibition of DHET formation by the soluble epoxide hydrolase inhibitor, 12(-3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA). TCDD also suppressed formation of mitochondrial and microsomal 20-HETE. The findings newly identify mitochondria as a site of P450-dependent arachidonic acid metabolism and as a potential target for TCDD effects. They also demonstrate that mitochondria contain soluble epoxide hydrolase and underscore a role for CYP1A in endobiotic metabolism.

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Section: Discussionmentioning

confidence: 54%

Mitochondrial P450-dependent arachidonic acid metabolism by TCDD-induced hepatic CYP1A5; conversion of EETs to DHETs by mitochondrial soluble epoxide hydrolase

Labitzke¹,

Diani-Moore²,

Rifkind³

2007

Archives of Biochemistry and Biophysics

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“…This enzyme has been localized to peroxisomes, in addition to cytoplasm and ER (Waechter et al 1983;Pahan et al 1996). It enables peroxisomes to convert arene or alkene oxides to dihydrodioles thus catabolizing fatty acids with an oxirane ring which are formed in sterol metabolism.…”

Section: Epoxide Hydrolasementioning

confidence: 96%

Mammalian peroxisomes and reactive oxygen species

Schrader

Fahimi

2004

Histochem Cell Biol

155

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The central role of peroxisomes in the generation and scavenging of hydrogen peroxide has been well known ever since their discovery almost four decades ago. Recent studies have revealed their involvement in metabolism of oxygen free radicals and nitric oxide that have important functions in intra- and intercellular signaling. The analysis of the role of mammalian peroxisomes in a variety of physiological and pathological processes involving reactive oxygen species (ROS) is the subject of this review. The general characteristics of peroxisomes and their enzymes involved in the metabolism of ROS are briefly reviewed. An expansion of the peroxisomal compartment with proliferation of tubular peroxisomes is observed in cells exposed to UV irradiation and various oxidants and is apparently accompanied by upregulation of PEX genes. Significant reduction of peroxisomes and their enzymes is observed in inflammatory processes including infections, ischemia-reperfusion injury, and allograft rejection and seems to be related to the suppressive effect of tumor necrosis factor-alpha on peroxisome function and peroxisome proliferator activated receptor-alpha. Xenobiotic-induced proliferation of peroxisomes in rodents is accompanied by the formation of hepatic tumors, and evidently the imbalance in generation and decomposition of ROS plays an important role in this process. In PEX5-/- knockout mice lacking functional peroxisomes severe alterations of mitochondria in various organs are observed which seem to be due to a generalized increase in oxidative stress confirming the important role of peroxisomes in homeostasis of ROS and the implications of its disturbances for cell pathology.

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“…Subsequent experiments in mice using isopycnic subfractionation and enzyme markers revealed both a peroxisomal and cytosolic localization (Waechter et al 1983;Kaur and Gill 1986). This was followed, however, by immunocytochemical experiments showing the localization of sEH solely in peroxisomes of mouse and rat liver.…”

mentioning

confidence: 99%

Cell-specific Subcellular Localization of Soluble Epoxide Hydrolase in Human Tissues

Enayetallah

French

Barber

et al. 2006

J Histochem Cytochem.

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Soluble epoxide hydrolase (sEH) is a phase-I xenobiotic metabolizing enzyme having both an N-terminal phosphatase activity and a C-terminal epoxide hydrolase activity. Endogenous hydrolase substrates include arachidonic acid epoxides, which have been involved in regulating blood pressure and inflammation. The subcellular localization of sEH has been controversial. Earlier studies using mouse and rat liver suggested that sEH may be cytosolic and/or peroxisomal. In this study we applied immunofluorescence and confocal microscopy using markers for different subcellular compartments to evaluate sEH colocalization in an array of human tissues. Results showed that sEH is both cytosolic and peroxisomal in human hepatocytes and renal proximal tubules and exclusively cytosolic in other sEH-containing tissues such as pancreatic islet cells, intestinal epithelium, anterior pituitary cells, adrenal gland, endometrium, lymphoid follicles, prostate ductal epithelium, alveolar wall, and blood vessels. sEH was not exclusively peroxisomal in any of the tissues evaluated. Our data suggest that human sEH subcellular localization is tissue dependent, and that sEH may have tissue- or cell-type-specific functionality. To our knowledge, this is the first report showing the subcellular localization of sEH in a wide array of human tissues.

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Epoxide hydrolase activity in isolated peroxisomes of mouse liver

Cited by 54 publications

References 14 publications

Mitochondrial P450-dependent arachidonic acid metabolism by TCDD-induced hepatic CYP1A5; conversion of EETs to DHETs by mitochondrial soluble epoxide hydrolase

Mitochondrial P450-dependent arachidonic acid metabolism by TCDD-induced hepatic CYP1A5; conversion of EETs to DHETs by mitochondrial soluble epoxide hydrolase

Mammalian peroxisomes and reactive oxygen species

Cell-specific Subcellular Localization of Soluble Epoxide Hydrolase in Human Tissues

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