cDNA Cloning, Heterologous Expression, and Characterization of Rat Intestinal CYP2J4

Zhang, Qing Yu; Ding, Xinxin; Kaminsky, Laurence S.

doi:10.1006/abbi.1997.9922

Cited by 39 publications

(47 citation statements)

References 22 publications

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“…CYP2J subfamily members have been identified in many species, including rabbits, rats, mice, and humans (Kikuta et al, 1991;Zhang et al, 1997;Nelson, 2009). The majority of P450s are primarily expressed in the liver, but the mouse CYP2J subfamily includes members that have a wide tissue distribution.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Four New Mouse Cytochrome P450 Enzymes of the CYP2J Subfamily

et al. 2013

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The cytochrome P450 superfamily encompasses a diverse group of enzymes that catalyze the oxidation of various substrates. The mouse CYP2J subfamily includes members that have wide tissue distribution and are active in the metabolism of arachidonic acid (AA), linoleic acid (LA), and other lipids and xenobiotics. The mouse Cyp2j locus contains seven genes and three pseudogenes located in a contiguous 0.62 megabase cluster on chromosome 4. We describe four new mouse CYP2J isoforms (designated CYP2J8, CYP2J11, CYP2J12, and CYP2J13). The four cDNAs contain open reading frames that encode polypeptides with 62-84% identity with the three previously identified mouse CYP2Js. All four new CYP2J proteins were expressed in Sf21 insect cells. Each recombinant protein metabolized AA and LA to epoxides and hydroxy derivatives. Specific antibodies, mRNA probes, and polymerase chain reaction primer sets were developed for each mouse CYP2J to examine their tissue distribution. CYP2J8 transcripts were found in the kidney, liver, and brain, and protein expression was confirmed in the kidney and brain (neuropil). CYP2J11 transcripts were most abundant in the kidney and heart, with protein detected primarily in the kidney (proximal convoluted tubules), liver, and heart (cardiomyocytes). CYP2J12 transcripts were prominently present in the brain, and CYP2J13 transcripts were detected in multiple tissues, with the highest expression in the kidney. CYP2J12 and CYP2J13 protein expression could not be determined because the antibodies developed were not immunospecific. We conclude that the four new CYP2J isoforms might be involved in the metabolism of AA and LA to bioactive lipids in mouse hepatic and extrahepatic tissues.

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Section: Introductionmentioning

confidence: 99%

Characterization of Four New Mouse Cytochrome P450 Enzymes of the CYP2J Subfamily

et al. 2013

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“…Recently, CYP2J4 was identified and found to be predominantly expressed in rat small intestine (Zhang et al, 1997a(Zhang et al, , 1998(Zhang et al, , 1999a. CYP2J4 has activities toward arachidonic acid and generates retinoic acid from retinal.…”

Section: Rat and Mouse Small Intestinal P450 Expressionmentioning

confidence: 99%

The Small Intestine as a Xenobiotic-Metabolizing Organ

Kaminsky

Zhang²

2003

Drug Metab Dispos

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“…Holla et al (11) showed that recombinant CYP2C11, CYP2C23, and CYP2C24, in that order, have the highest-to-lowest expoxygenase activity. Similarly, recombinant rat CYP2J3 and CYP2J4 are active in the metabolism of AA to EETs (25,36,38). Renal epoxygenase profiles and antibody inhibition studies have established that CYP2C23 is the predominant AA epoxygenase in the rat kidney (11).…”

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confidence: 99%

Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats

Huang

Morisseau²,

Wang³

et al. 2007

American Journal of Physiology-Renal Physiology

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Hammock BD, Wang M-H. Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats. Am J Physiol Renal Physiol 293: F342-F349, 2007. First published April 18, 2007; doi:10.1152/ajprenal.00004.2007.-Since epoxyeicosatrienoic acids (EETs) affect sodium reabsorption in renal tubules and dilate the renal vasculature, we have examined their effects on renal hemodynamics and sodium balance in male rats fed a high-fat (HF) diet by fenofibrate, a peroxisome proliferator-activated receptor-␣ (PPAR-␣) agonist and an inducer of cytochrome P-450 (CYP) epoxygenases; by N-methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH), a selective EET biosynthesis inhibitor; and by 12-(3-adamantane-1-yl-ureido)dodecanoic acid (AUDA), a selective inhibitor of soluble epoxide hydrolase. In rats treated with fenofibrate (30 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ig) or AUDA (50 mg/l in drinking water) for 2 wk, mean arterial pressure, renal vascular resistance, and glomerular filtration rate were lower but renal blood flow was higher than in vehicle-treated control rats. In addition, fenofibrate and AUDA decreased cumulative sodium balance in the HF rats. Treatment with MSPPOH (20 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 iv) ϩ fenofibrate for 2 wk reversed renal hemodynamics and sodium balance to the levels in control HF rats. Moreover, fenofibrate caused a threefold increase in renal cortical CYP epoxygenase activity, whereas the fenofibrate-induced elevation of this activity was attenuated by MSPPOH. Western blot analysis showed that fenofibrate induced the expression of CYP epoxygenases in renal cortex and microvessels and that the induction effect of fenofibrate was blocked by MSPPOH. These results demonstrate that the fenofibrate-induced increase of CYP epoxygenase expression and the AUDA-induced stabilization of EET production in the kidneys cause renal vascular dilation and reduce sodium retention, contributing to the improvement of abnormal renal hemodynamics and hypertension in HF rats. obesity; cytochrome P-450; arachidonic acid; eicosanoid; kidney CYTOCHROME P-450 (CYP) enzymes constitute a major metabolic pathway for arachidonic acid (AA). In the presence of NADPH and oxygen, AA is epoxidized by the CYP enzyme system to give four epoxyeicosatrienoic acids (EETs): 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET. The EETs are hydrolyzed by soluble epoxide hydrolase (sEH) to the corresponding vic-dihydroxyeicosatrienoic acids (DHETs) (14,21,24).EET biosynthesis can be carried out by several CYP isoforms, including the CYP1A, CYP2B, CYP2C, CYP2D, CYP2E, and CYP2J families (24). Although many CYP enzymes can epoxidize AA, it has been demonstrated that CYP2C and CYP2J are primarily responsible for renal EET formation. Holla et al. (11) showed that recombinant CYP2C11, CYP2C23, and CYP2C24, in that order, have the highest-to-lowest expoxygenase activity. Similarly, recombinant rat CYP2J3 and CYP2J4 are active in the metabolism of AA to EETs (25,36,38). Renal epoxygenase profiles and antibody inhibit...

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cDNA Cloning, Heterologous Expression, and Characterization of Rat Intestinal CYP2J4

Cited by 39 publications

References 22 publications

Characterization of Four New Mouse Cytochrome P450 Enzymes of the CYP2J Subfamily

Characterization of Four New Mouse Cytochrome P450 Enzymes of the CYP2J Subfamily

The Small Intestine as a Xenobiotic-Metabolizing Organ

Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats

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