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20-HETE

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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
#1
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...
October 17, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29018033/expression-and-functional-characterization-of-breast-cancer-associated-cytochrome-p450-4z1-in-saccharomyces-cerevisiae
#2
Matthew G McDonald, Sutapa Ray, Clara J Amorosi, Katherine A Sitko, John P Kowalski, Lorela Paco, Abhinav Nath, Byron M Gallis, Rheem A Totah, Maitreya J Dunham, Douglas M Fowler, Allan E Rettie
CYP4Z1 is an 'orphan' P450 enzyme that has provoked interest because of its hypothesized role in breast cancer through formation of the signaling molecule 20-HETE. We expressed human CYP4Z1 in Saccharomyces cerevisiae and evaluated its catalytic capabilities towards 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, while the 12-hydroxy metabolite was not detected...
October 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28994119/naturally-occurring-%C3%AF-hydroxyacids
#3
REVIEW
Philip 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 water proofing and signaling. The purpose of this review is 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...
October 10, 2017: International Journal of Cosmetic Science
https://www.readbyqxmd.com/read/28951873/multiple-targets-for-novel-therapy-of-fsgs-associated-with-circulating-permeability-factor
#4
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
#5
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...
September 22, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28940693/hyperbaric-oxygenation-and-20-hete-inhibition-reduce-stroke-volume-in-female-diabetic-sprague-dawley-rats
#6
Mihael Mišir, Marija Renić, Sanja Novak, Martina Mihalj, Anita Ćosić, Monika Vesel, Ines Drenjančević
We evaluated the effects of acute and repetitive hyperbaric oxygenation (HBO2 ), 20-HETE inhibition by N-hydroxy-N'-(4-butyl-2methylphenyl)-formamidine (HET0016) and their combinations on experimental stroke outcomes. Streptozotocin-induced type-1 diabetic Sprague-Dawley female rats (N = 42, N = 7/group), were subjected to 30' transient middle cerebral artery occlusion (t-MCAO) / reperfusion and divided in following groups; (a) Control group, without treatment; and groups exposed to: (b) HBO2 ; (c) multiple HBO2 (HBO2 immediately and second exposure 12 h after t-MCAO); (d) HET0016 pretreatment (1 mg kg(-1) /3 days prior to t-MCAO) combined with HBO2 after t-MCAO; (e) HET0016 treatment (1 h before, during and for 6 hours after t-MCAO); and (f) HET0016 treatment followed by HBO2 after t-MCAO...
September 21, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28912346/the-blood-pressure-lowering-effect-of-20-hete-blockade-in-cyp4a14-mice-is-associated-with-natriuresis
#7
Varunkumar Pandey, Victor Garcia, Ankit Gilani, Priyanka Mishra, Frank Fan Zhang, Mahesh P Paudyal, John R Falck, Alberto Nasjletti, Wen-Hui Wang, Michal L Schwartzman
20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) has been linked to pro- and anti-hypertensive actions through its ability to promote vasoconstriction and inhibit Na transport in the ascending limb of the loop of Henle, respectively. In this study, we assessed the effects of 20-HETE blockade on blood pressure, renal hemodynamics and urinary sodium excretion in Cyp4a14(-/-) male mice, which display androgen-driven 20-HETE-dependent hypertension. Administration of 20-SOLA, a water-soluble 20-HETE antagonist, in the drinking water normalized blood pressure of male Cyp4a14(-/-) hypertensive mice (124± vs 153± mmHg) while having no effect on age-matched normotensive wild-type male mice...
September 14, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28899749/cyp4a-cyp2c-modulation-of-the-interaction-of-calcium-channel-blockers-with-cyclosporine-on-edhf-mediated-renal-vasodilations-in-rats
#8
Safaa H Hammoud, Amal G Omar, Assaad A Eid, Mahmoud M El-Mas
The endothelium-derived hyperpolarizing factor (EDHF) serves as a back-up mechanism that compensates for reduced nitric oxide (NO)/prostanoids bioavailability. Here we investigated whether (i) under conditions of vascular endothelium dysfunction, the immunosuppressant drug cyclosporine (CSA) upregulates EDHF-dependent renal vasodilations through altering CYP4A/CYP2C signaling, and (ii) calcium channel blockers modulate the CSA/EDHF/CYP interaction. Rats were treated with CSA, verapamil, nifedipine, or their combinations for 7days...
November 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28807746/20-hete-regulated-psmb5-expression-via-tgf-%C3%AE-smad-signaling-pathway
#9
Guangrui Lai, Ru Sun, Jingjing Wu, Bijun Zhang, Yanyan Zhao
We previously found that 20-hydroxyeicosatetraeonic acid (20-HETE) showed an effect on proteasome activity in cytochrome P450 F2 (CYP4F2) transgenic mice. Proteasome subunit β5 (PSMB5) is a primary subunit of the proteasome. In the current study, we examine whether 20-HETE has any affect on PSMB5. We found that PSMB5 was upregulated in the liver, but downregulated in the kidney of transgenic mice, when compared with wild-type mice. Luciferase reporter gene experiments and electrophoretic mobility shift assays (EMSA) suggested that Smad3 directly associated with the putative Smad binding element (SBE) of the Psmb5 promoter...
August 11, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28768289/%C3%AE-adrenergic-receptor-stimulated-cardiac-myocyte-apoptosis-role-of-cytochrome-p450-%C3%AF-hydroxylase
#10
Shan Jiang, Dan Huo, Xueying Wang, Huan Zhao, Jiang Tan, Qinghua Zeng, Stephen T OʼRourke, Chengwen Sun
Prolonged or excessive β-adrenergic activation leads to cardiac myocyte loss and heart dysfunction; however, the underlying cellular mechanisms are still unclear. Therefore, we first confirmed the effect of isoproterenol (ISO), a β-adrenergic receptor agonist, on cardiac toxicity using TUNEL and caspase activity assays in cultured rat cardiomyocytes. ISO treatment significantly increased cardiomyocyte apoptosis. Persistent ISO stimulation of cardiomyocytes also increased the expression of CYP4A3, a major CYP450 ω-hydroxylase that produces 20-hydroxyeicosatetraenoic acid (20-HETE) in a time-dependent manner...
August 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28767146/a-randomized-trial-of-effects-of-alcohol-on-cytochrome-p450-eicosanoids-mediators-of-inflammation-resolution-and-blood-pressure-in-men
#11
Anne E Barden, Venus Chavez, Michael Phillips, Emilie Mas, Lawrence J Beilin, Kevin D Croft, Trevor A Mori, Ian B Puddey
BACKGROUND: Cardiovascular effects of alcohol consumption may be influenced by both pro- and anti-inflammatory mechanisms. We previously showed that chronic alcohol consumption increased blood pressure (BP), oxidative stress, and 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor and pro-inflammatory eicosanoid synthesized by cytochrome P450 (CYP450) enzymes from arachidonic acid. This study in men examined the effect of consuming red wine (RW) on BP in relation to changes in 20-HETE, oxidative stress (F2 -isoprostanes), markers of inflammation, anti-inflammatory CYP450 epoxyeicosatrienoic acids (EETs), and specialized pro-resolving mediators of inflammation (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)...
August 2, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28646793/shexiang-baoxin-pills-promotes-angiogenesis-in-myocardial-infarction-rats-via-up-regulation-of-20-hete-mediated-endothelial-progenitor-cells-mobilization
#12
Feifei Huang, Yang Liu, Xia Yang, Di Che, Kaifeng Qiu, Bruce D Hammock, Jingfeng Wang, Mong-Heng Wang, Jie Chen, Hui Huang
BACKGROUND AND AIMS: Therapeutic angiogenesis is a pivotal strategy for ischemic heart disease. The aim of the present study was to determine the effect and molecular mechanism of Shexiang Baoxin pills, a widely-used traditional Chinese medicine for ischemic heart disease, on angiogenesis in a rat model of myocardial infarction (MI). METHODS: We used the occlusion of left anterior descending coronary artery of Sprague-Dawley rats as a model of MI. The MI rats were treated with distilled water, Shexiang Baoxin pills, or Shexiang Baoxin pills + HET0016 (a selective blocker of the biosynthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) at 10 mg/kg/day), respectively...
June 7, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28641720/fenofibrate-attenuates-hypertension-in-goldblatt-hypertensive-rats-role-of-20-hydroxyeicosatetraenoic-acid-in-the-nonclipped-kidney
#13
Alexandra Sporková, Věra Čertíková Chábová, Šárka Doleželová, Šárka Jíchová, Libor Kopkan, Zdeňka Vaňourková, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Hana Maxová, Luděk Červenka
BACKGROUND: There is vast evidence that the renin-angiotensin system is not the sole determinant of blood pressure (BP) elevation in human renovascular hypertension or the relevant experimental models. This study tested the hypothesis that kidney deficiency of 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent ω-hydroxylase pathway of arachidonic acid metabolism, is important in the pathophysiology of the maintenance phase of 2-kidney, 1-clip (2K1C) Goldblatt hypertension...
June 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28639228/role-of-20-hydroxyeicosatetraenoic-acid-20-hete-in-androgen-mediated-cell-viability-in-prostate-cancer-cells
#14
Cecilia Colombero, Daniela Papademetrio, Paula Sacca, Eduardo Mormandi, Elida Alvarez, Susana Nowicki
20-Hydroxyeicosatetraenoic acid (20-HETE) is generated intracellularly through the ω-hydroxylation of arachidonic acid by the cytochrome P450 (in humans, CYP4A11 and CYP4F2). 20-HETE induces mitogenic responses in different cancer cells. The aim of this study was to analyze how 20-HETE impacts cell survival, proliferation, and apoptosis in prostate cancer cells. Incubation of the human androgen-sensitive cells (LNCaP) with 1-10 μM HET0016 (a selective inhibitor of 20-HETE synthesis) reduced cell viability by 49*-64%* (*p < 0...
August 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28609459/het0016-decreases-lung-metastasis-from-breast-cancer-in-immune-competent-mouse-model
#15
Thaiz F Borin, Adarsh Shankar, Kartik Angara, Mohammad H Rashid, Meenu Jain, Asm Iskander, Roxan Ara, Iryna Lebedyeva, Hasan Korkaya, Bhagelu R Achyut, Ali S Arbab
Distant metastasis is the primary cause of death in the majority of the cancer types. Recently, much importance has been given to tumor microenvironment (TME) in the development of invasive malignant tumors, as well as the metastasis potential. The ability of tumor cells to modulate TME and to escape immune-mediated attack by releasing immunosuppressive cytokines has become a hallmark of breast cancer. Our study shows the effect of IV formulation of HET0016 (HPßCD-HET0016) a selective inhibitor of 20-HETE synthesis, administered intravenously in immune-competent in vivo mouse model of murine breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28602979/inhibition-of-cyp4a-by-a-novel-flavonoid-fla-16-prolongs-survival-and-normalizes-tumor-vasculature-in-glioma
#16
Chenlong Wang, Ying Li, Honglei Chen, Jie Zhang, Jing Zhang, Tian Qin, Chenfan Duan, Xuewei Chen, Yanzhuo Liu, Xiaoyang Zhou, Jing Yang
Glioblastomas rapidly become refractory to anti-VEGF therapies. We previously showed that cytochrome P450 (CYP) 4A-derived 20-hydroxyeicosatetraenoic acid (20-HETE) promotes angiogenesis. Here, we tested whether a novel flavonoid (FLA-16) prolongs survival and normalizes tumor vasculature in glioma through CYP4A inhibition. FLA-16 improved survival, reduced tumor burden, and normalized vasculature, accompanied with the decreased secretion of 20-HETE, VEGF and TGF-β in tumor-associated macrophages (TAMs) and endothelial progenitor cells (EPCs) in C6 and U87 gliomas...
August 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28546348/gpr75-identified-as-the-first-20-hete-receptor-a-chemokine-receptor-adopted-by-a-new-family
#17
EDITORIAL
Fan Fan, Richard J Roman
No abstract text is available yet for this article.
May 26, 2017: Circulation Research
https://www.readbyqxmd.com/read/28533430/heme-thiolate-sulfenylation-of-human-cytochrome-p450-4a11-functions-as-a-redox-switch-for-catalytic-inhibition
#18
Matthew E Albertolle, Donghak Kim, Leslie D Nagy, Chul-Ho Yun, Ambra Pozzi, Üzen Savas, Eric F Johnson, F Peter Guengerich
Cytochrome P450 (P450, CYP) 4A11 is a human fatty acid ω-hydroxylase that catalyzes the oxidation of arachidonic acid to the eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE), which plays important roles in regulating blood pressure regulation. Variants of P450 4A11 have been associated with high blood pressure and resistance to anti-hypertensive drugs, and 20-HETE has both pro- and antihypertensive properties relating to increased vasoconstriction and natriuresis, respectively. These physiological activities are likely influenced by the redox environment, but the mechanisms are unclear...
July 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28533146/bioactive-lipids-derived-from-arachidonic-acid-metabolism-in-different-types-of-renal-replacement-therapy
#19
Joanna Stępniewska, Barbara Dołęgowska, Kamila Puchałowicz, Edyta Gołembiewska, Kazimierz Ciechanowski
INTRODUCTION: Metabolism and plasma concentration of lipids and lipid-derived compounds play an important role in kidney physiology and pathological processes. The component of membrane phospholipids - arachidonic acid (AA) and its active derivatives - eicosanoids are involved in the development of hypertension, diabetes, inflammation and may contribute to progression of chronic kidney disease (CKD). The purpose of the study was to determine, whether the type of renal replacement therapy has an effect on eicosanoids metabolism...
August 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28525367/liposomal-co-delivered-oleanolic-acid-attenuates-doxorubicin-induced-multi-organ-toxicity-in-hepatocellular-carcinoma
#20
Muhammad Sarfraz, Attia Afzal, Shahid Masood Raza, Sajid Bashir, Asadullah Madni, Muhammad Waseem Khan, Xiang Ma, Guangya Xiang
Doxorubicin in combination with other cytotoxic drugs has clinical advantages. However, doxorubicin-induced cardiotoxicity negatively impacts clinical utility and outcomes. Cardiotoxicity can result from increased oxidative stress or from a local cytochrome P450 mediated increase in 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE). Oleanolic acid (OA) is a natural pentacyclic triterpenoid with free radical scavenging, cardioprotective, and P450-mediated cyclooxygenase-upregulating properties. We investigated co-delivery of liposomal OA and doxorubicin in a HepG2 model of hepatocellular carcinoma (HCC)...
July 18, 2017: Oncotarget
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