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https://www.readbyqxmd.com/read/29427791/cyp2j2-derived-eets-attenuated-ethanol-induced-myocardial-dysfunction-through-inducing-autophagy-and-reducing-apoptosis
#1
Chi Zhou, Jin Huang, Qing Li, Chenao Zhan, Xizhen Xu, Xu Zhang, Ding Ai, Yi Zhu, Zheng Wen, Dao Wen Wang
Chronic excessive drinking leads to myocardial contractile dysfunction and dilated cardiomyopathy, where ethanol toxicity plays an essential role. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acids to form epoxyeicosatrienoic acids (EETs), which exert beneficial roles in the cardiovascular system, but their role in alcoholic cardiomyopathy is elusive. This study was designed to evaluate the effects and mechanisms of CYP2J2 gene delivery on ethanol-induced myocardial dysfunction with focus on autophagy and apoptosis...
February 7, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29394279/characterisation-of-the-vasodilation-effects-of-dha-and-epa-n-3-pufas-fish-oils-in-rat-aorta-and-mesenteric-resistance-arteries
#2
Roshan Limbu, Graeme S Cottrell, Alister J McNeish
BACKGROUND AND PURPOSE: Increasing evidence suggests that the omega-3 polyunsaturated acids (n-3 PUFA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are beneficial to cardiovascular health, promoting relaxation of vascular smooth muscle cells and vasodilation. Numerous studies have attempted to study these responses, but to date there has not been a systematic characterisation of both DHA and EPA mediated vasodilation in conduit and resistance arteries. Therefore, we aimed to fully characterise the n-3 PUFA-induced vasodilation pathways in rat aorta and mesenteric artery...
2018: PloS One
https://www.readbyqxmd.com/read/29361048/role-of-the-cytochrome-p-450-epoxyeicosatrienoic-acids-pathway-in-the-pathogenesis-of-renal-dysfunction-in-cirrhosis
#3
Michael M Yeboah, Md Abdul Hye Khan, Marla A Chesnik, Melissa Skibba, Lauren L Kolb, John D Imig
Background: Hepatorenal syndrome (HRS) is a life-threatening complication of advanced liver cirrhosis that is characterized by hemodynamic alterations in the kidney and other vascular beds. Cytochrome P(CYP)-450 enzymes metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acids. These eicosanoids regulate blood pressure, vascular tone and renal tubular sodium transport under both physiological and pathophysiological states. Methods: Experiments were performed to investigate the role of the CYP system in the pathogenesis of renal dysfunction during cirrhosis...
January 19, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29318723/endothelium-specific-cyp2j2-overexpression-attenuates-age-related-insulin-resistance
#4
Yan Yang, Ruolan Dong, Zhihui Chen, Danli Hu, Menglu Fu, Ying Tang, Dao Wen Wang, Xizhen Xu, Ling Tu
Ample evidences demonstrate that cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti-inflammatory, and cardiovascular protective effects. In this study, we investigated the effects of endothelium-specific CYP2J2 overexpression on age-related insulin resistance and metabolic dysfunction. Endothelium-specific targeting of the human CYP epoxygenase, CYP2J2, transgenic mice (Tie2-CYP2J2-Tr mice) was utilized. The effects of endothelium-specific CYP2J2 overexpression on aging-associated obesity, inflammation, and peripheral insulin resistance were evaluated by assessing metabolic parameters in young (3 months old) and aged (16 months old) adult male Tie2-CYP2J2-Tr mice...
January 10, 2018: Aging Cell
https://www.readbyqxmd.com/read/29298899/epoxide-hydrolase-1-ephx1-hydrolyzes-epoxyeicosanoids-and-impairs-cardiac-recovery-after-ischemia
#5
Matthew L Edin, Behin Gholipour Hamedani, Artiom Gruzdev, Joan P Graves, Fred B Lih, Samuel J Arbes, Rohanit Singh, Anette C Orjuela Leon, J Alyce Bradbury, Laura M DeGraff, Samantha L Hoopes, Michael Arand, Darryl Zeldin
Stimuli such as inflammation or hypoxia induce cytochrome P450 epoxygenase-mediated production of arachidonic acid-derived epoxyeicosatrienoic acids (EETs). EETs have cardioprotective, vasodilatory, angiogenic, anti-inflammatory, and analgesic effects, which are diminished by EET hydrolysis yielding biologically less active dihydroxyeicosatrienoic acids (DHETs). Previous in vitro assays have suggested that epoxide hydrolase 2 (EPHX2) is responsible for nearly all EET hydrolysis; EPHX1, which exhibits slow EET hydrolysis in vitro, is thought to contribute only marginally to EET hydrolysis...
January 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29290096/protective-effect-of-fenofibrate-against-ischemia-reperfusion-induced-cardiac-arrhythmias-in-isolated-rat-hearts
#6
Ishfaq A Bukhari, Abdulrahman A Almotrefi, Osama Y Mohamed, Abeer A Al-Masri, Saeed Ahmed Sheikh
Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α activator that lowers triglycerides and influences cytochrome P-450 (CYP-450) epoxygenase dependent arachidonic acid (AA) metabolism. CYP-450 epoxygenase metabolizes AA to epoxyeicosatrienoic acids (EETs). EETs have coronary dilating, cardiac and renal protective properties. Fibrates possess similar properties due to their CYP-450 epoxygenase inducing properties that leads to increase in endogenous EETs production. In the current investigations fenofibrate (100 mg/kg, orally) for two weeks decreased ischemia/reperfusion (I/R)-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT) and ventricular fibrillation (VF) in the isolated rat hearts...
December 31, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29243191/pharmacologically-induced-impairment-of-neurovascular-coupling-responses-alters-gait-coordination-in-mice
#7
Stefano Tarantini, Andriy Yabluchanksiy, Gábor A Fülöp, Peter Hertelendy, M Noa Valcarcel-Ares, Tamas Kiss, Jonathan M Bagwell, Daniel O'Connor, Eszter Farkas, Farzaneh Sorond, Anna Csiszar, Zoltan Ungvari
There is correlative evidence that impaired cerebral blood flow (CBF) regulation, in addition to promoting cognitive impairment, is also associated with alterations in gait and development of falls in elderly people. CBF is adjusted to neuronal activity via neurovascular coupling (NVC) and this mechanism becomes progressively impaired with age. To establish a direct cause-and-effect relationship between impaired NVC and gait abnormalities, we induced neurovascular uncoupling pharmacologically in young C57BL/6 mice by inhibiting the synthesis of vasodilator mediators involved in NVC...
December 14, 2017: GeroScience
https://www.readbyqxmd.com/read/29236467/recent-advances-in-enzymatic-complexity-generation-cyclization-reactions
#8
Christopher T Walsh, Yi Tang
Enzymes in biosynthetic pathways, especially in plant and microbial metabolism, generate structural and functional group complexity in small molecules by conversion of acyclic frameworks to cyclic scaffolds in short, efficient routes. The distinct chemical logic used by several distinct classes of cyclases, oxidative and non-oxidative, has recently been elucidated by genome mining, heterologous expression, and genetic and mechanistic analyses. These include enzymes carrying out pericyclic transformations, pyran synthases, tandem acting epoxygenases and epoxide "hydrolases", as well as oxygenases and radical SAM enzymes that involve rearrangements of substrate radicals under aerobic or anaerobic conditions, respectively...
December 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/29158256/heart-failure-induced-activation-of-phospholipase-ipla2%C3%AE-%C3%A2-generates-hydroxyeicosatetraenoic-acids-opening-the-mitochondrial-permeability-transition-pore
#9
Sung Ho Moon, Xinping Liu, Ari M Cedars, Kui Yang, Michael A Kiebish, Susan M Joseph, John Kelley, Christopher M Jenkins, Richard W Gross
Congestive heart failure typically arises from cardiac myocyte necrosis/apoptosis, associated with the pathological opening of the mitochondrial permeability transition pore (mPTP). mPTP opening decreases the mitochondrial membrane potential leading to the activation of Ca(2+)-independent phospholipase A2γ (iPLA2γ) and the production of downstream toxic metabolites. However, the array of enzymatic mediators and the exact chemical mechanisms responsible for modulating myocardial mPTP opening remain unclear...
November 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29081082/epoxyeicosatrienoic-acid-inhibits-the-apoptosis-of-cerebral-microvascular-smooth-muscle-cells-by-oxygen-glucose-deprivation-via-targeting-the-jnk-c-jun-and-mtor-signaling-pathways
#10
Youyang Qu, Yu Liu, Yanmei Zhu, Li Chen, Wei Sun, Yulan Zhu
As a component of the neurovascular unit, cerebral smooth muscle cells (CSMCs) are an important mediator in the development of cerebral vascular diseases such as stroke. Epoxyeicosatrienoic acids (EETs) are the products of arachidonic acid catalyzed by cytochrome P450 epoxygenase. EETs are shown to exert neuroprotective effects. In this article, the role of EET in the growth and apoptosis of CSMCs and the underlying mechanisms under oxygen glucose deprivation (OGD) conditions were addressed. The viability of CMSCs was decreased significantly in the OGD group, while different subtypes of EETs, especially 14,15-EET, could increase the viability of CSMCs under OGD conditions...
October 27, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/29080699/therapeutic-potential-of-omega-3-fatty-acid-derived-epoxyeicosanoids-in-cardiovascular-and-inflammatory-diseases
#11
REVIEW
Wolf-Hagen Schunck, Anne Konkel, Robert Fischer, Karsten-Henrich Weylandt
Numerous benefits have been attributed to dietary long-chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFAs), including protection against cardiac arrhythmia, triglyceride-lowering, amelioration of inflammatory, and neurodegenerative disorders. This review covers recent findings indicating that a variety of these beneficial effects are mediated by "omega-3 epoxyeicosanoids", a class of novel n-3 LC-PUFA-derived lipid mediators, which are generated via the cytochrome P450 (CYP) epoxygenase pathway. CYP enzymes, previously identified as arachidonic acid (20:4n-6; AA) epoxygenases, accept eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA), the major fish oil n-3 LC-PUFAs, as efficient alternative substrates...
November 7, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29071994/-effect-of-jiaji-ex-b-2-electroacupuncture-preconditioning-on-expression-of-cytochrome-p-450-signaling-pathways-in-myocardial-ischemia-reperfusion-rats
#12
Yang Li, Ming-Lu Shao, Hui-Juan Yu, Qi-Wen Tan, Hua-Feng Cui
OBJECTIVE: To investigate the effect of "Jiaji"(EX-B 2)-electroacupuncture(EA) preconditioning on the myocardium and expression of cytochrome P 450 signaling pathways of myocardial cells in myocardial ischemia-reperfusion injury(MI/RI) rats. METHODS: Sixty male Wistar rats were randomly divided into sham operation, model, Jiaji, Neiguan(PC 6), Yanglingquan(GB 34) and Quchi(LI 11) groups (n=10 in each group). MI/RI model was established by occlusion of the descen-ding anterior branch of the left coronary artery...
February 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29050342/role-of-the-cyp3a4-mediated-11-12-epoxyeicosatrienoic-acid-pathway-in-the-development-of-tamoxifen-resistant-breast-cancer
#13
Nguyen Thi Thuy Phuong, Ji Won Kim, Jung-Ae Kim, Jang Su Jeon, Ji-Yoon Lee, Wen Jun Xu, Jin Won Yang, Sang Kyum Kim, Keon Wook Kang
Epoxyeicosatrienoic acid (EET) production via cytochrome P450 (CYP) epoxygenases closely correlates with the progression of breast cancer. However, its role in the development of chemoresistant breast cancers has yet to be elucidated. Here, we found that CYP3A4 expression and its epoxy-product, 11,12-epoxyeicosatrienoic acid (11,12-EET) was enhanced in tamoxifen (TAM)-resistant MCF-7 (TAMR-MCF-7) breast cancer cells compared to control MCF-7 cells. Treatment of TAMR-MCF-7 cells with ketoconazole and azamulin (selective CYP3A4 inhibitors) or 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an EET antagonist) inhibited cellular proliferation and recovered the sensitivity to 4-hydroxytamoxifen...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29022765/polymorphisms-in-genes-involved-in-vasoactive-eicosanoid-synthesis-affect-cardiovascular-risk-in-renal-transplant-recipients
#14
Guillermo Gervasini, Enrique Luna, Guadalupe Garcia-Pino, Lilia Azevedo, Sonia Mota-Zamorano, Juan José Cubero
OBJECTIVE: Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases leads to epoxyeicosatrienoic acids (EETs), which are eicosanoids with vasodilator and anti-inflammatory properties. We aim to determine whether genetic variability in these routes may contribute to cardiovascular (CV) risk in renal transplant recipients. METHODS: In a cohort of 355 patients, we determined the presence of two polymorphisms, CYP2C8*3 and CYP2J2*7, known to affect eicosanoid levels...
November 8, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28975360/beyond-detoxification-a-role-for-mouse-meh-in-the-hepatic-metabolism-of-endogenous-lipids
#15
Anne Marowsky, Imke Meyer, Kira Erismann-Ebner, Giovanni Pellegrini, Nandkishor Mule, Michael Arand
Microsomal and soluble epoxide hydrolase (mEH and sEH) fulfill apparently distinct roles: Whereas mEH detoxifies xenobiotics, sEH hydrolyzes fatty acid (FA) signaling molecules and is thus implicated in a variety of physiological functions. These epoxy FAs comprise epoxyeicosatrienoic acids (EETs) and epoxy-octadecenoic acids (EpOMEs), which are formed by CYP epoxygenases from arachidonic acid (AA) and linoleic acid, respectively, and then are hydrolyzed to their respective diols, the so-called DHETs and DiHOMEs...
October 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28937442/orally-active-epoxyeicosatrienoic-acid-analogs
#16
William B Campbell, John D Imig, James M Schmitz, John R Falck
Biologically active epoxyeicosatrienoic acid (EET) regioisomers are synthesized from arachidonic acid by cytochrome P450 epoxygenases of endothelial, myocardial, and renal tubular cells. EETs relax vascular smooth muscle and decrease inflammatory cell adhesion and cytokine release. Renal EETs promote sodium excretion and vasodilation to decrease hypertension. Cardiac EETs reduce infarct size after ischemia-reperfusion injury and decrease fibrosis and inflammation in heart failure. In diabetes, EETs improve insulin sensitivity, increase glucose tolerance, and reduce the renal injury...
October 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28919040/heme-binding-biguanides-target-cytochrome-p450-dependent-cancer-cell-mitochondria
#17
Zhijun Guo, Irina F Sevrioukova, Ilia G Denisov, Xia Zhang, Ting-Lan Chiu, Dafydd G Thomas, Eric A Hanse, Rebecca A D Cuellar, Yelena V Grinkova, Vanessa Wankhede Langenfeld, Daniel S Swedien, Justin D Stamschror, Juan Alvarez, Fernando Luna, Adela Galván, Young Kyung Bae, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Beverly Norris, Craig M Flory, Robert J Schumacher, M Gerard O'Sullivan, Qing Cao, Haitao Chu, John D Lipscomb, William M Atkins, Kalpna Gupta, Ameeta Kelekar, Ian A Blair, Jorge H Capdevila, John R Falck, Stephen G Sligar, Thomas L Poulos, Gunda I Georg, Elizabeth Ambrose, David A Potter
The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs...
October 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28881620/eets-reduces-lps-induced-hyperpermeability-by-targeting-grp78-mediated-src-activation-and-subsequent-rho-rock-signaling-pathway
#18
Ruolan Dong, Danli Hu, Yan Yang, Zhihui Chen, Menglu Fu, Dao Wen Wang, Xizhen Xu, Ling Tu
Integrity of endothelial barrier is a determinant of the prognosis in the acute lung injury caused by sepsis. The epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, exhibit protective effects in various pathogenic states, however, whether EETs play a role in endothelial barrier enhancement and the involved mechanisms remain to be investigated. Here, we show that increased EETs level by endothelial specific cytochrome P450 epoxygenase 2J2 over-expression and soluble epoxide hydrolase (sEH) inhibitor TPPU reduced lipopolysaccharide-induced endothelial hyper-permeability in vivo, accompanied by improved survival of septic mice...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877879/uninephrectomy-and-apical-fluid-shear-stress-decrease-enac-abundance-in-collecting-duct-principal-cells
#19
Thomas Ernandez, Khalil Udwan, Alexandra Chassot, Pierre-Yves Martin, Eric Feraille
Acute nephron reduction such as after living kidney donation may increase the risk of hypertension. Uninephrectomy induces major hemodynamic changes in the remaining kidney resulting in rapid increase of single nephron GFR and fluid delivery in the distal nephron. Decreased sodium (Na) fractional reabsorption after the distal tubule has been reported after uninephrectomy in animals preserving volume homeostasis. In the present study, we thought to specifically explore the effect of unilateral nephrectomy on ENaC subunits expression in mice...
September 6, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28842441/carotid-artery-stenosis-in-hypertensive-rats-impairs-dilatory-pathways-in-parenchymal-arterioles
#20
Nusrat Matin, Courtney Fisher, William F Jackson, Janice M Diaz-Otero, Anne M Dorrance
Hypertension is a leading risk factor for vascular cognitive impairment and is strongly associated with carotid artery stenosis. In normotensive rats, chronic cerebral hypoperfusion induced by bilateral common carotid artery stenosis (BCAS) leads to cognitive impairment that is associated with impaired endothelium-dependent dilation in parenchymal arterioles (PAs). The aim of this study was to assess the effects of BCAS on PA function and structure in stroke prone spontaneously hypertensive rats (SHRSP), a model of human essential hypertension...
August 25, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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