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20-HETE

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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
#1
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
#2
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
#3
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
#4
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
#5
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...
June 7, 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
#6
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
#7
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
#8
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
#9
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)...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28347661/functional-characterization-of-a-common-cyp4f11-genetic-variant-and-identification-of-functionally-defective-cyp4f11-variants-in-erythromycin-metabolism-and-20-hete-synthesis
#10
Myeongjin Yi, Sun-Ah Cho, Jungki Min, Dong Hyun Kim, Jae-Gook Shin, Su-Jun Lee
CYP4F11, together with CYP4F2, plays an important role in the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid. We identified 21 variants by whole exome sequencing, including 4 non-synonymous variants in Korean subjects. The proteins of the wild-type CYP4F11 and the four coding variants (C276R, D315N, D374Y, and D446N) were expressed in Escherichia coli DH5α cells and purified to give cytochrome P450-specific carbon monoxide difference spectra. Wild-type CYP4F2 was also expressed and purified to compare its activity with the CYP4F11 wild-type...
April 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28325781/20-hete-signals-through-g-protein-coupled-receptor-gpr75-gq-to-affect-vascular-function-and-trigger-hypertension
#11
Victor Garcia, Ankit Gilani, Brian Shkolnik, Varunkumar Pandey, Frank Fan Zhang, Rambabu Dakarapu, Shyam K Gandham, N Rami Reddy, Joan P Graves, Artiom Gruzdev, Darryl C Zeldin, Jorge H Capdevila, John R Falck, Michal Laniado Schwartzman
RATIONALE: 20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 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...
May 26, 2017: Circulation Research
https://www.readbyqxmd.com/read/28249552/hypertension-induced-enhanced-myogenic-constriction-of-cerebral-arteries-is-preserved-after-traumatic-brain-injury
#12
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 from pressure/volume overload; however, 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...
April 26, 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
#13
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
#14
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)...
January 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
#15
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
#16
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
#17
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...
February 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28011587/elevated-20-hete-impairs-coronary-collateral-growth-in-metabolic-syndrome-via-endothelial-dysfunction
#18
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 MetS (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)...
March 1, 2017: 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
#19
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...
September 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/27933871/food-polyphenol-apigenin-inhibits-the-cytochrome-p450-monoxygenase-branch-of-the-arachidonic-acid-cascade
#20
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
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