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20-HETE

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https://www.readbyqxmd.com/read/29886242/conflicting-roles-of-20-hete-in-hypertension-and-renal-end-organ-damage
#1
REVIEW
Chao Zhang, George W Booz, Qing Yu, Xiaochen He, Shaoxun Wang, Fan Fan
20-HETE is a cytochrome P450-derived metabolite of arachidonic acid that has both pro- and anti-hypertensive actions that result from modulation of vascular and kidney function. In the vasculature, 20-HETE sensitizes vascular smooth muscle cells to constrictor stimuli and increases myogenic tone. By promoting smooth muscle cell migration and proliferation, as well as by acting on the vascular endothelium to cause endothelial dysfunction, angiotensin converting enzyme (ACE) expression, and inflammation, 20-HETE contributes to adverse vascular remodeling and increased blood pressure...
June 7, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29867542/detrimental-effects-of-testosterone-addition-to-estrogen-therapy-involve-cytochrome-p-450-induced-20-hete-synthesis-in-aorta-of-ovariectomized-spontaneously-hypertensive-rat-shr-a-model-of-postmenopausal-hypertension
#2
Tiago J Costa, Graziela S Ceravolo, Cinthya Echem, Carolina M Hashimoto, Beatriz P Costa, Rosangela A Santos-Eichler, Maria Aparecida Oliveira, Francesc Jiménez-Altayó, Eliana H Akamine, Ana Paula Dantas, Maria Helena C Carvalho
Postmenopausal period has been associated to different symptoms such as hot flashes, vulvovaginal atrophy, hypoactive sexual desire disorder (HSDD) and others. Clinical studies have described postmenopausal women presenting HSDD can benefit from the association of testosterone to conventional hormonal therapy. Testosterone has been linked to development of cardiovascular diseases including hypertension and it also increases cytochrome P -450-induced 20-HETE synthesis which in turn results in vascular dysfunction...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29760152/20-hete-hypertension-and-beyond
#3
REVIEW
Richard J Roman, Fan Fan
No abstract text is available yet for this article.
May 14, 2018: Hypertension
https://www.readbyqxmd.com/read/29698447/celecoxib-use-and-circulating-oxylipins-in-a-colon-polyp-prevention-trial
#4
Jessica A Martinez, Jun Yang, Betsy C Wertheim, Denise J Roe, Alexander Schriewer, Peter Lance, David S Alberts, Bruce D Hammock, Patricia A Thompson
Drugs that inhibit cyclooxygenase (COX)-2 and the metabolism of arachidonic acid (ARA) to prostaglandin E2 are potent anti-inflammatory agents used widely in the treatment of joint and muscle pain. Despite their benefits, daily use of these drugs has been associated with hypertension, cardiovascular and gastrointestinal toxicities. It is now recognized that ARA is metabolized to a number of bioactive oxygenated lipids (oxylipins) by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes...
2018: PloS One
https://www.readbyqxmd.com/read/29628049/identification-of-novel-cyp4f2-genetic-variants-exhibiting-decreased-catalytic-activity-in-the-conversion-of-arachidonic-acid-to-20-hydroxyeicosatetraenoic-acid-20-hete
#5
Woo-Young Kim, Su-Jun Lee, Jungki Min, Kyung-Suk Oh, Dong-Hyun Kim, Heui-Soo Kim, Jae-Gook Shin
CYP4F2 is an enzyme involved in the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid and metabolizes vitamin K into an inactive form. Our objectives were to identify new CYP4F2 genetic variants and to characterize the functional consequences of the conversion of arachidonic acid into 20-HETE. We used direct DNA sequencing to identify a total of 20 single-nucleotide polymorphisms (SNPs) including four coding variants, A27V, R47C, P85A, and V433M, in 50 randomly selected subjects. Of these, A27V and P85A were new...
April 2018: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/29625729/corrigendum-to-elevated-20-hete-in-metabolic-syndrome-regulates-arterial-stiffness-and-systolic-hypertension-via-mmp12-activation-j-mol-cell-cardiol-117-2018-88-99
#6
Amanda Soler, Ian Hunter, Gregory Joseph, Rebecca Hutcheson, Brenda Hutcheson, Jenny Yang, Frank Fan Zhang, Sachindra Raj Joshi, Chastity Bradford, Katherine H Gotlinger, Rachana Maniyar, John R Falck, Spencer Proctor, Michal Laniado Schwartzman, Sachin A Gupte, Petra Rocic
No abstract text is available yet for this article.
April 4, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29588191/arachidonic-acid-metabolites-of-cyp4a-and-cyp4f-are-altered-in-women-with-preeclampsia
#7
Nicole L Plenty, Jessica L Faulkner, Joshua Cotton, Shauna-Kay Spencer, Kedra Wallace, Babbette LaMarca, Sydney R Murphy
Few studies exist on cytochrome P450 (CYP450) metabolites of arachidonic acid (AA) pertaining to the pathophysiological events in pregnancy. We hypothesized that metabolism of AA via the CYP450 pathways is altered within the placenta in women with preeclampsia (PE) and contributes to the pathophysiology of the disease. Thus, placental vascular CYP450 enzyme expression and activity were measured in normal pregnant (NP) and preeclamptic (PE) patients. CYP450 isoform expression (CYP4A11, CYP4A22, CYP4F2, and CYP4F3) was found to be elevated within the placenta of women with PE compared to normal pregnant (NP) women and chronic hypertensive (CHTN) pregnant women...
May 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29568904/roles-of-elevated-20%C3%A2-hete-in-the-breakdown-of-blood-brain-barrier-and-the-severity-of-brain-edema-in-experimental-traumatic-brain-injury
#8
Liyan Lu, Mingliang Wang, Fang Yuan, Xiaoer Wei, Wenbin Li
Breakdown of the blood brain barrier (BBB) is a secondary injury following traumatic brain injury (TBI) and can lead to the development of brain edema. However, the factors that contribute to the disruption of the BBB and increase the severity of brain edema in TBI remain to be elucidated. 20‑hydroxyeicosatetraenoic acid (20‑HETE) is a metabolite of arachidonic acid. The inhibition of 20‑HETEsynthesis by HET0016 has been suggested as a strategy to decrease brain edema. The present study aimed to investigate whether the elevated production of 20‑HETE in cerebral tissue may contribute to BBB breakdown and increase the severity of brain edema in rats with TBI...
May 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29485354/20-hete-synthesis-inhibition-promotes-cerebral-protection-after-intracerebral-hemorrhage-without-inhibiting-angiogenesis
#9
Xiaoning Han, Xiaochun Zhao, Xi Lan, Qian Li, Yufeng Gao, Xi Liu, Jieru Wan, Zengjin Yang, Xuemei Chen, Weidong Zang, Austin M Guo, John R Falck, Raymond C Koehler, Jian Wang
20-HETE, an arachidonic acid metabolite synthesized by cytochrome P450 4A, plays an important role in acute brain damage from ischemic stroke or subarachnoid hemorrhage. We tested the hypothesis that 20-HETE inhibition has a protective effect after intracerebral hemorrhage (ICH) and then investigated its effect on angiogenesis. We exposed hippocampal slice cultures to hemoglobin and induced ICH in mouse brains by intrastriatal collagenase injection to investigate the protective effect of 20-HETE synthesis inhibitor N-hydroxy-N'-(4- n-butyl-2-methylphenyl)-formamidine (HET0016)...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29465314/endogenously-generated-arachidonate-derived-ligands-for-trpv1-induce-cardiac-protection-in-sepsis
#10
Jianmin Chen, Alexander J P Hamers, Michaela Finsterbusch, Gianmichele Massimo, Maleeha Zafar, Roger Corder, Romain A Colas, Jesmond Dalli, Christoph Thiemermann, Amrita Ahluwalia
The severity of cardiac dysfunction predicts mortality in sepsis. Activation of transient receptor potential vanilloid receptor type (TRPV)-1, a predominantly neuronal nonselective cation channel, has been shown to improve outcome in sepsis and endotoxemia. However, the role of TRPV1 and the identity of its endogenous ligands in the cardiac dysfunction caused by sepsis and endotoxemia are unknown. Using TRPV1-/- and TRPV1+/+ mice, we showed that endogenous activation of cardiac TRPV1 during sepsis is key to limiting the ensuing cardiac dysfunction...
February 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29428638/elevated-20-hete-in-metabolic-syndrome-regulates-arterial-stiffness-and-systolic-hypertension-via-mmp12-activation
#11
Amanda Soler, Ian Hunter, Gregory Joseph, Rebecca Hutcheson, Brenda Hutcheson, Jenny Yang, Frank Fan Zhang, Sachindra Raj Joshi, Chastity Bradford, Katherine H Gotlinger, Rachana Maniyar, John R Falck, Spencer Proctor, Michal Laniado Schwartzman, Sachin A Gupte, Petra Rocic
Arterial stiffness plays a causal role in development of systolic hypertension. 20-hydroxyeicosatetraeonic acid (20-HETE), a cytochrome P450 (CYP450)-derived arachidonic acid metabolite, is known to be elevated in resistance arteries in hypertensive animal models and loosely associated with obesity in humans. However, the role of 20-HETE in the regulation of large artery remodeling in metabolic syndrome has not been investigated. We hypothesized that elevated 20-HETE in metabolic syndrome increases matrix metalloproteinase 12 (MMP12) activation leading to increased degradation of elastin, increased large artery stiffness and increased systolic blood pressure...
April 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29414682/the-hete-is-on-ffar1-and-pancreatic-islet-cells
#12
Mette Trauelsen, Michael Lückmann, Thomas M Frimurer, Thue W Schwartz
It is known but generally unappreciated that the fatty acid receptor FFAR1 (GPR40) is responsible for a major part of glucose-induced insulin secretion. This puzzling fact is now explained by Tunaru et al. (2018), who demonstrate that glucose-induced 20-hydroxyeicosatetraenoic acid (20-HETE) amplifies insulin secretion through autocrine activation of FFAR1.
February 6, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29330456/20-hete-promotes-glucose-stimulated-insulin-secretion-in-an-autocrine-manner-through-ffar1
#13
Sorin Tunaru, Remy Bonnavion, Isabell Brandenburger, Jens Preussner, Dominique Thomas, Klaus Scholich, Stefan Offermanns
The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic β-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in β-cells remains poorly understood. Here we show that 20-HETE activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than dietary fatty acids such as palmitic, linoleic, and α-linolenic acid. Murine and human β-cells produce 20-HETE, and the ω-hydroxylase-mediated formation and release of 20-HETE is strongly stimulated by glucose...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29277328/induction-of-cytochrome-p450-4a14-contributes-to-angiotensin-ii-induced-renal-fibrosis-in-mice
#14
Yunfeng Zhou, Jingwei Yu, Jia Liu, Rong Cao, Wen Su, Sha Li, Shiqi Ye, Chenggang Zhu, Xiaolin Zhang, Hu Xu, Hua Chen, Xiaoyan Zhang, Youfei Guan
Angiotensin II (AngII) plays an important role in the pathogenesis of hypertension and associated renal injuries. To elucidate the molecular mechanism by which AngII induces renal damage, we found that AngII infusion significantly induced CYP4A14 expression in renal proximal tubule cells (RPTCs) with marked increases in blood pressure and proteinuria. Renal production of the major CYP4A metabolite, 20-HETE, was also significantly increased in the AngII-treated mice. Compared to wild-type (WT) mice, CYP4A14 knockout (CYP4A14-/- ) mice exhibited significantly lower levels of blood pressure, renal 20-HETE production, proteinuria and renal fibrosis following AngII infusion...
March 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29206843/periparturient-lipolysis-and-oxylipid-biosynthesis-in-bovine-adipose-tissues
#15
G Andres Contreras, Clarissa Strieder-Barboza, Jonas de Souza, Jeff Gandy, Vengai Mavangira, Adam L Lock, Lorraine M Sordillo
The periparturient period of dairy cows is characterized by intense lipolysis in adipose tissues (AT), which induces the release of free fatty acids (FFA) into circulation. Among FFA, polyunsaturated fatty acids are susceptible to oxidation and can modulate inflammatory responses during lipolysis within AT. Linoleic and arachidonic acid oxidized products (oxylipids) such as hydroxy-octadecadienoic acids (HODE) and hydroxy-eicosatetraenoic acids (HETE), were recently identified as products of lipolysis that could modulate AT inflammation during lipolysis...
2017: PloS One
https://www.readbyqxmd.com/read/29039560/20-hydroxyeicosatetraenoic-acid-regulates-the-expression-of-nedd4%C3%A2-2-in-kidney-and-liver-through-a-neddylation-modification-pathway
#16
Jianzhu Zhao, Bijun Zhang, Guangrui Lai, Runhong Xu, Guoming Chu, Yanyan Zhao
The present study aimed to test whether 20-hydroxyeicosatetraenoic acid (20‑HETE) affected neddylation modification of E3‑ligase Nedd4‑2 (neural precursor cell expressed, developmentally down‑regulated 4‑like, E3 ubiquitin protein ligase). A cytochrome P450 family 4 subfamily F member 2 (CYP4F2) transgenic mouse model that overproduces 20‑HETE in the kidney and the liver was used in the present study. Transgenic mice with high salt intake exhibited increased activation of Nedd4‑2‑mediated ubiquitin‑proteasome pathway...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29018033/expression-and-functional-characterization-of-breast-cancer-associated-cytochrome-p450-4z1-in-saccharomyces-cerevisiae
#17
Matthew G McDonald, Sutapa Ray, Clara J Amorosi, Katherine A Sitko, John P Kowalski, Lorela Paco, Abhinav Nath, Byron Gallis, Rheem A Totah, Maitreya J Dunham, Douglas M Fowler, Allan E Rettie
CYP4Z1 is an "orphan" cytochrome P450 (P450) enzyme that has provoked interest because of its hypothesized role in breast cancer through formation of the signaling molecule 20-hydroxyeicosatetraenoic acid (20-HETE). We expressed human CYP4Z1 in Saccharomyces cerevisiae and evaluated its catalytic capabilities toward arachidonic and lauric acids (AA and LA). Specific and sensitive mass spectrometry assays enabled discrimination of the regioselectivity of hydroxylation of these two fatty acids. CYP4Z1 generated 7-, 8-, 9-, 10-, and 11-hydroxy LA, whereas the 12-hydroxy metabolite was not detected...
December 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28994119/naturally-occurring-%C3%AF-hydroxyacids
#18
REVIEW
P W Wertz
ω-Hydroxyacids are fatty acids bearing a hydroxyl group on the terminal carbon. They are found in mammals and higher plants and are often involved in providing a permeability barrier, the primary purpose of which is to reduce water loss. Some ω-hydroxyacid derivatives may be involved in waterproofing and signalling. The purpose of this review was to survey the known natural sources of ω-hydroxyacids. ω-Hydroxyacids are produced by two different P450-dependent mechanisms. The longer (30-34 carbons) ω-hydroxyacids are produced by chain extension from palmitic acid until the chain extends across the membrane in which the extension is taking place, and then the terminal carbon is hydroxylated...
February 2018: International Journal of Cosmetic Science
https://www.readbyqxmd.com/read/28951873/multiple-targets-for-novel-therapy-of-fsgs-associated-with-circulating-permeability-factor
#19
REVIEW
Virginia J Savin, Mukut Sharma, Jianping Zhou, David Genochi, Ram Sharma, Tarak Srivastava, Amna Ilahe, Pooja Budhiraja, Aditi Gupta, Ellen T McCarthy
A plasma component is responsible for altered glomerular permeability in patients with focal segmental glomerulosclerosis. Evidence includes recurrence after renal transplantation, remission after plasmapheresis, proteinuria in infants of affected mothers, transfer of proteinuria to experimental animals, and impaired glomerular permeability after exposure to patient plasma. Therapy may include decreasing synthesis of the injurious agent, removing or blocking its interaction with cells, or blocking signaling or enhancing cell defenses to restore the permeability barrier and prevent progression...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28951260/selective-inhibition-of-20-hydroxyeicosatetraenoic-acid-lowers-blood-pressure-in-a-rat-model-of-preeclampsia
#20
Jessica L Faulkner, Nicole L Plenty, Kedra Wallace, Lorena M Amaral, Mark W Cunningham, Sydney Murphy, Babbette LaMarca
Little is currently known of the role(s) of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) in hypertensive pregnancies. We hypothesized that specific inhibition of 20-HETE would attenuate increases in blood pressure in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. Specific 20-HETE synthesis inhibitor HET0016 (1mg/kg) was administered daily to RUPP rats from gestational days 14-18. Blood pressure (BP) increased in RUPP rats and was decreased with HET0016 administration...
January 2018: Prostaglandins & Other Lipid Mediators
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