Determination of major UDP-glucuronosyltransferase enzymes and their genotypes responsible for 20-HETE glucuronidation

Jarrar, Yazun; Cha, Eun-Young; Seo, Kyung-Ah; Ghim, Jong-Lyul; Kim, Hyo-Ji; Kim, Dong-Hyun; Lee, Su-Jun; Shin, Jae‐Gook

doi:10.1194/jlr.m051169

Cited by 23 publications

(20 citation statements)

References 35 publications

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“…20-HETE is inactivated via metabolism by COX 2 to 20-hydroxy-PGE 1 (8, 43, 44) and alcohol dehydrogenase to 20-carboxy-eicosatetraenoic acid (20-COOH-HETE) followed by metabolism by beta-oxidation to 18- and 16-carbon dicarboxylic acids (25, 45). Circulating 20-HETE is conjugated in the liver by uridine 5′-diphosphoglucuronosyltransferase (UGT) to a glucuronide (46, 47) that is filtered and excreted in the urine (48). …”

Section: Introductionmentioning

confidence: 99%

“…It is also produced in the cerebral vasculature, glial cells and neurons, and is associated with ischemic and hemorrhagic stroke and brain injury. Recent human studies have indicated that sequence variants in CYP4A11 (28, 31, 98–110) and CYP4F2 (99, 110–115) that produce 20-HETE as well as UGT that is involved in the biotransformation of 20-HETE (46), are all associated with hypertension and/or stroke.…”

Section: Introductionmentioning

confidence: 99%

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Molecular mechanisms in differentiated thyroid cancer

2016

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Cytochrome P450s enzymes catalyze the metabolism of arachidonic acid to epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid and hydroxyeicosatetraeonic acid (HETEs). 20-HETE is a vasoconstrictor that depolarizes vascular smooth muscle cells by blocking K+ channels. EETs serve as endothelial derived hyperpolarizing factors. Inhibition of the formation of 20-HETE impairs the myogenic response and autoregulation of renal and cerebral blood flow. Changes in the formation of EETs and 20-HETE have been reported in hypertension and drugs that target these pathways alter blood pressure in animal models. Sequence variants in CYP4A11 and CYP4F2 that produce 20-HETE, UDP-glucuronosyl transferase involved in the biotransformation of 20-HETE and soluble epoxide hydrolase that inactivates EETs are associated with hypertension in human studies. 20-HETE contributes to the regulation of vascular hypertrophy, restenosis, angiogenesis and inflammation. It also promotes endothelial dysfunction and contributes to cerebral vasospasm and ischemia-reperfusion injury in the brain, kidney and heart. This review will focus on the role of 20-HETE in vascular dysfunction, inflammation, ischemic and hemorrhagic stroke and cardiac and renal ischemia reperfusion injury.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms in differentiated thyroid cancer

2016

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“…Studies of genetic variations indicate that UGT1A9 and UGT2B7 appear to be major UGT enzymes responsible for 20-HETE and LTB4 glucuronidation (Fig. 1B) [34]. Urinary 20-HETE glucuronide excretion is high in patients with liver cirrhosis M a n u s c r i p t 6 [35].…”

Section: Eicosanoidsmentioning

confidence: 98%

Roles of human UDP-glucuronosyltransferases in clearance and homeostasis of endogenous substrates, and functional implications

Bock

2015

Biochemical Pharmacology

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“…The 802C>T variant on UGT2B7 gene is a non-synonymous exonic genetic variant leads to the substitution of histidine to tyrosine in codon 268 [7]. Although in vitro study showed that UGT2B7*2 802C>T genetic variant increased the UGT2B7 activity, multiple in vivo clinical studies reported that UGT2B7*2 genotyped volunteers had less UGT2B7 activity than the wild type [8]. In comparison with the wild type UGT2B7 genotype, it has been shown that UGT2B7*2 genotype altered clinically the metabolism and drug response of epirubicin, morphine and diclofenac [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…In comparison with the wild type UGT2B7 genotype, it has been shown that UGT2B7*2 genotype altered clinically the metabolism and drug response of epirubicin, morphine and diclofenac [9][10][11][12]. The UGT2B7*2 allele was also found to affect the conjugation of the endogenous arachidonic acid metabolite; 20-hydroxyeicosatetraeonic acid which may contribute the variation in the cardiovascular homeostasis [8].…”

Section: Introductionmentioning

confidence: 99%

The Frequency of UGT2B7*2 (802C>T) Allele among Healthy Unrelated Jordanian Volunteers

YB¹,

Kherfan²,

Obaid³

2016

J Drug Metab Toxicol

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The UDP-Glucuronesyl Transferase (UGT) 2B7*2 802C>T is the most common functional genetic variant on UGT2B7 gene with reported influence on drug response. Objective: To determine the frequency of UGT2B7*2 (802C>T) genetic variant among Jordanian population. Methods: The DNA samples from 90 healthy Jordanian volunteers were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism assays (PCR-RFLP) to determine the UGT2B7*2 allele. Results: The frequency (95% confidence interval) of UGT2B7*2 802C allele was 0.59 (0.52 to 0.66) and for UGT2B7*2 802T was 0.41 (0.34 to 0.48), which was similar to the Caucasian but different than African ethnic populations. The UGT2B7 genotype frequency among Jordanians was 0.31 (0.22 to 0.4) for wild, 0.57(0.47 to 0.67) for heterozygote and 0.12 (0.06 to 0.18) for homozygote UGT2B7*2 genotype. Conclusion: This study reported for the first time the UGT2B7*2 frequency and genotype profile among Jordanians. The findings of this study will increase our understanding in explaining the inter-individual variation in drug response among Jordanian population.

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Determination of major UDP-glucuronosyltransferase enzymes and their genotypes responsible for 20-HETE glucuronidation

Cited by 23 publications

References 35 publications

Molecular mechanisms in differentiated thyroid cancer

Molecular mechanisms in differentiated thyroid cancer

Roles of human UDP-glucuronosyltransferases in clearance and homeostasis of endogenous substrates, and functional implications

The Frequency of UGT2B7*2 (802C>T) Allele among Healthy Unrelated Jordanian Volunteers

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