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20-HETE

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https://www.readbyqxmd.com/read/28325781/hete-signals-through-g-protein-coupled-receptor-gpr75-gq-to-affect-vascular-function-and-trigger-hypertension
#1
Victor Garcia, Ankit Gilani, Brian Shkolnik, Varunkumar Pandey, Frank F Zhang, Rambabu Dakarapu, Shyam K Gandham, N R Reddy, Joan P Graves, Artiom Gruzdev, Darryl C Zeldin, Jorge H Capdevila, John R Falck, Michal L Schwartzman
Rationale: 20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 (CYP) eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration and proliferation, as well as endothelial cell dysfunction and inflammation. Increased levels of 20-HETE in experimental animals and in humans are associated with hypertension, stroke, myocardial infarction and vascular diseases. Objective: To date, a receptor/binding site for 20-HETE has been implicated based on the use of specific agonists and antagonists...
March 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28249552/hypertension-induced-enhanced-myogenic-constriction-of-cerebral-arteries-is-preserved-after-traumatic-brain-injury
#2
Nikolett Szarka, Krisztina Amrein, Peter Horvath, Ivan Ivic, Endre Czeiter, Andras Buki, Akos Koller, Peter Toth
Traumatic brain injury (TBI) was shown to impair pressure-induced myogenic response of cerebral arteries, which is associated with vascular and neural dysfunction and increased mortality of TBI patients. Hypertension was shown to enhance myogenic tone of cerebral arteries via increased vascular production of 20-hydroxyeicosatrienoic acid (HETE). This adaptive mechanism protects brain tissue form pressure/volume overload, but it can also lead to increased susceptibility to cerebral ischemia. Although both effects may potentiate the detrimental vascular consequences of TBI, it is not known how hypertension modulates the effect of TBI on myogenic responses of cerebral vessels...
March 1, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28230738/clinical-implications-of-20-hydroxyeicosatetraenoic-acid-in-the-kidney-liver-lung-and-brain-an-emerging-therapeutic-target
#3
REVIEW
Osama H Elshenawy, Sherif M Shoieb, Anwar Mohamed, Ayman O S El-Kadi
Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport...
February 20, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28132967/kidney-cadmium-toxicity-diabetes-and-high-blood-pressure-the-perfect-storm
#4
REVIEW
Soisungwan Satarug, David A Vesey, Glenda C Gobe
Cadmium (Cd) is an environmental toxicant of widespread exposure and pervasive toxicity. Absorption, systemic transport and uptake of Cd are mediated by metal transporters that the body uses for acquisition of physiologically-essential elements, notably of iron, zinc and calcium. Currently, human exposure to Cd is known to damage the kidneys, especially the proximal tubular cells that actively reabsorb Cd along with zinc, glucose and amino acids in the glomerular filtrate. Severe kidney damage, glycosuria and proteinuria are known outcomes after high dietary Cd intake (> 200 µg/day)...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28110484/upregulation-of-20-hete-synthetic-cytochrome-p450-isoforms-by-oxygen-glucose-deprivation-in-cortical-neurons
#5
Hui Zhang, John R Falck, Richard J Roman, David R Harder, Raymond C Koehler, Zeng-Jin Yang
20-Hydroxyeicosatetraenoic acid (20-HETE), a potent vasoconstrictor, is a cytochrome P450 (CYP) 4A/4F-derived metabolite of arachidonic acid. Inhibition of 20-HETE synthesis protects brain from ischemic injury. However, that protection is not associated with changes in cerebral blood flow. The present study examined whether CYP4A isoforms are expressed in neurons, whether they produce 20-HETE in neurons, and whether neuronally derived 20-HETE exerts direct neurotoxicity after oxygen-glucose deprivation (OGD)...
January 21, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28039371/granular-layer-neurons-control-cerebellar-neurovascular-coupling-through-an-nmda-receptor-no-dependent-system
#6
Lisa Mapelli, Giuseppe Gagliano, Teresa Soda, Umberto Laforenza, Francesco Moccia, Egidio D'Angelo
Neurovascular coupling (NVC) is the process whereby neuronal activity controls blood vessel diameter. In the cerebellum, the molecular layer is regarded as the main NVC determinant. However, the granular layer is a region with variable metabolic demand caused by large activity fluctuations, that shows a prominent expression of NMDA receptors (NMDARs) and nitric oxide synthase (NOS) and is therefore much more suitable for effective NVC. Here we show that, in the granular layer of acute rat cerebellar slices, capillary diameter rapidly changes following mossy fiber stimulation...
December 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28025003/chemical-synthesis-and-biological-evaluation-of-%C3%AF-hydroxy-polyunsaturated-fatty-acids
#7
Sung Hee Hwang, Karen Wagner, Jian Xu, Jun Yang, Xichun Li, Zhengyu Cao, Christophe Morisseau, Kin Sing Stephen Lee, Bruce D Hammock
ω-Hydroxy polyunsaturated fatty acids (PUFAs), natural metabolites from arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were prepared via convergent synthesis approach using two key steps: Cu-mediated CC bond formation to construct methylene skipped poly-ynes and a partial alkyne hydrogenation where the presence of excess 2-methyl-2-butene as an additive that is proven to be critical for the success of partial reduction of the poly-ynes to the corresponding cis-alkenes without over-hydrogenation...
December 2, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28011587/elevated-20-hete-impairs-coronary-collateral-growth-in-metabolic-syndrome-via-endothelial-dysfunction
#8
Gregory Joseph, Amanda Soler, Rebecca Hutcheson, Ian Hunter, Chastity Bradford, Brenda Hutcheson, Katherine H Gotlinger, Houli Jiang, John R Falck, Spencer Proctor, Michal Laniado Schwartzman, Petra Rocic
Coronary collateral growth (CCG) is impaired in metabolic syndrome (MetS). microRNA-145 (miR-145-Adv) delivery to our rat model of metabolic syndrome (JCR) completely restored and neutrophil depletion significantly improved CCG. We determined whether low endogenous levels of miR-145 in MetS allowed for elevated production of 20-hydroxyeicosatetraenoic acid (20-HETE), which in turn, resulted in excessive neutrophil accumulation and endothelial dysfunction leading to impaired CCG. Rats underwent 0-9 days of repetitive ischemia (RI)...
December 23, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27990624/vascular-mimicry-in-glioblastoma-following-anti-angiogenic-and-anti-20-hete-therapies
#9
Kartik Angara, Mohammad H Rashid, Adarsh Shankar, Roxan Ara, Asm Iskander, Thaiz F Borin, Meenu Jain, Bhagelu R Achyut, Ali S Arbab
Glioblastoma (GBM) is one hypervascular and hypoxic tumor known among solid tumors. Antiangiogenic therapeutics (AATs) have been tested as an adjuvant to normalize blood vessels and control abnormal vasculature. Evidence of relapse exemplified in the progressive tumor growth following AAT reflects development of resistance to AATs. Here, we identified that GBM following AAT (Vatalanib) acquired an alternate mechanism to support tumor growth, called vascular mimicry (VM). We observed that Vatalanib induced VM vessels are positive for periodic acid-Schiff (PAS) matrix but devoid of any endothelium on the inner side and lined by tumor cells on the outer-side...
December 19, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27933871/food-polyphenol-apigenin-inhibits-the-cytochrome-p450-monoxygenase-branch-of-the-arachidonic-acid-cascade
#10
Maryvonne Steuck, Stefan Hellhake, Nils Helge Schebb
The product of cytochrome P450 monooxygenase (P450) ω-hydroxylation of arachidonic acid (AA), 20- hydroxyeicosatetraenoic acid (HETE), is a potent vasoconstrictor. Utilizing microsomes as well as individual CYP4 isoforms we demonstrate here that flavonoids can block 20-HETE formation. Apigenin inhibits CYP4F2 with an IC50 value of 4.6 μM and 20-HETE formation in human liver and kidney microsomes at 2.4-9.8 μM. Interestingly, the structurally similar naringenin shows no relevant effect on the formation of 20-HETE...
November 30, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27916259/cyp-genetic-variants-cyp-metabolite-levels-and-neurologic-deterioration-in-acute-ischemic-stroke-in-chinese-population
#11
Xingyang Yi, Jing Lin, Chun Wang, Qiang Zhou
BACKGROUND: The mechanisms of neurologic deterioration (ND) are not fully understood. The aim of the present study was to evaluate the relationship between CYP genetic variants and CYP metabolite levels with ND in acute ischemic stroke patients. METHODS: Eleven single nucleotide polymorphisms (SNPs) of seven CYP genes were genotyped in 396 patients with acute ischemic stroke. The CYP plasma metabolite levels (20-hydroxyeicosatetraenoic acid [HETE], total epoxyeicosatrienoic acids [EETs], and dihydroxyeicosatrienoic acids [DiHETEs]) were also assessed...
December 1, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/27916218/fenofibrate-attenuates-malignant-hypertension-by-suppression-of-the-renin-angiotensin-system-a-study-in-cyp1a1-ren-2-transgenic-rats
#12
Šárka Jíchová, Šárka Doleželová, Libor Kopkan, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Luděk Červenka
BACKGROUND: Malignant hypertension is a life-threatening condition, and its pathophysiology is still poorly understood. The present study was designed to evaluate the role of interaction of the renin-angiotensin system with 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent ω-hydroxylase pathway, in the pathophysiology of angiotensin II (ANG II)-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. METHODS: Malignant hypertension was induced by 12 days׳ dietary administration of 0...
December 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27906746/recent-developments-on-the-vascular-effects-of-20-hydroxyeicosatetraenoic-acid
#13
Victor Garcia, Michal L Schwartzman
PURPOSE OF REVIEW: 20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoactive eicosanoid and a key constituent of the microcirculation. Its effects on vascular function are multifaceted and include stimulation of smooth muscle, contractility, migration, and proliferation, as well as endothelial cell dysfunction and inflammation. Such effects have significant implications with regard to the control of vascular homeostasis and pathophysiology. The clinical relevance of 20-HETE is highlighted by recent studies linking 20-HETE and its biosynthetic enzymes to the development of hypertension, stroke, and myocardial infarction...
March 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27878278/alteration-of-epoxyeicosatrienoic-acids-in-the-liver-and-kidney-of-cytochrome-p450-4f2-transgenic-mice
#14
Bijun Zhang, Guangrui Lai, Xiaoliang Liu, Yanyan Zhao
Arachidonic acid (AA) can be metabolized into 20-hydroxyeicosatetraenoic acid (20-HETE) by ω-hydroxylases, and epoxyeicosatrienoic acids (EETs) by epoxygenases. The effects of EETs in cardiovascular physiology are vasodilatory, anti-inflammatory and anti‑apoptotic, which are opposite to the function to 20‑HETE. However, EETs are not stable in vivo, and are rapidly degraded to the biologically less active metabolites, dihydroxyeicosatrienoic acids, via soluble epoxide hydrolase (sEH). Western blotting, reverse transcription‑quantitative polymerase chain reaction and liquid chromatography tandem mass spectrometry were performed in order to determine target RNA and protein expression levels...
December 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27850407/769-sex-differences-in-response-to-20-hete-inhibition-after-traumatic-brain-injury-in-immature-rats
#15
Courtney Robertson, Manda Saraswati, Shiyu Su, Dawn Spicer, Raymond Koehler
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27834744/20-hydroxyeicosatetraenoic-acid-as-a-predictor-of-neurological-deterioration-in-acute-minor-ischemic-stroke
#16
Xingyang Yi, Zhao Han, Qiang Zhou, Jing Lin, Ping Liu
BACKGROUND AND PURPOSE: The relationship between high plasma 20-hydroxyeicosatetraenoic acid (20-HETE) levels and neurological deterioration (ND) has not been investigated in patients with acute minor ischemic stroke. METHOD: We conducted a prospective, multicenter observational study in patients with acute minor ischemic stroke. Plasma levels of 20-HETE were measured at admission in all patients. The primary end point of the study was ND within 10 days after admission...
December 2016: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/27630573/20-hydroxyeicosatetraenoic-acid-20-hete-modulates-canonical-transient-receptor-potential-6-trpc6-channels-in-podocytes
#17
Hila Roshanravan, Eun Y Kim, Stuart E Dryer
The arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) regulates renal function, including changes in glomerular function evoked during tubuloglomerular feedback (TGF). This study describes the cellular actions of 20-HETE on cultured podocytes, assessed by whole-cell recordings from cultured podocytes combined with pharmacological and cell-biological manipulations of cells. Bath superfusion of 20-HETE activates cationic currents that are blocked by the pan-TRP blocker SKF-96365 and by 50 μM La(3+), and which are attenuated after siRNA knockdown of TRPC6 subunits...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27596333/meloxicam-fails-to-augment-the-reno-protective-effects-of-soluble-epoxide-hydrolase-inhibition-in-streptozotocin-induced-diabetic-rats-via-increased-20-hete-levels
#18
Mohamed M Katary, Chelsey Pye, Ahmed A Elmarakby
The pro-inflammatory cyclooxygenase (COX)-derived prostaglandins and the anti-inflammatory cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of renal injury. The current study examined whether COX inhibition augments the reno-protective effects of increased EETs levels via inhibiting EETs degradation by soluble epoxide hydrolase (sEH) in diabetic rats. Streptozotocin (50mg/kg, i.v) was used to induce diabetes in male Sprague Dawley rats. Rats were then divided into 5 groups (n=6-8); control non diabetic, diabetic, diabetic treated with the sEH inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), diabetic treated with the COX inhibitor meloxicam and diabetic treated with meloxicam plus t-AUCB for 2 months...
September 2, 2016: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/27580276/the-cardioprotection-of-dihydrotanshinone-i-against-myocardial-ischemia-reperfusion-injury-via-inhibition-of-arachidonic-acid-%C3%AF-hydroxylase
#19
Yidan Wei, Meijuan Xu, Yi Ren, Guo Lu, Yangmei Xu, Yangyang Song, Hui Ji
Arachidonic acid (AA) is a precursor that is metabolized by several enzymes to many biological eicosanoids. Accumulating data indicate that the ω-hydroxylation metabolite of AA, 20-hydroxyeicosatetraenoic acid (20-HETE), is considered to be involved in the myocardial ischemia-reperfusion injury (MIRI). The inhibitors of AA ω-hydroxylase, however, are demonstrated to exhibit protective effects on MIRI. Dihydrotanshinone I (DI), a bioactive constituent of danshen, is proven to be a potent inhibitor of AA ω-hydroxylase by our preliminary study in vitro...
December 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27568038/20-hete-attenuates-the-response-of-glucose-stimulated-insulin-secretion-through-the-akt-gsk-3%C3%AE-glut2-pathway
#20
Bijun Zhang, Guangrui Lai, Jingjing Wu, Ru Sun, Runhong Xu, Xianghong Yang, Yafei Qi, Yanyan Zhao
We previously generated cytochrome P450 4F2 (CYP4F2) transgenic mice that have high levels of 20-hydroxyeicosatetraenoic acid (20-HETE) production; these mice exhibit both hypertension and hyperglycemia without insulin resistance. Currently, it is unclear whether and how 20-HETE affects insulin secretion, thus resulting in hyperglycemia. In this study, we found that 20-HETE attenuated glucose-stimulated insulin secretion (GSIS) in CYP4F2 transgenic mice as well as in rat insulinoma INS-1E cells treated with 0...
November 2016: Endocrine
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