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  1 / 1304 MEDLINE  
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[PMID]:29353041
[Au] Autor:Hayashi Y; Shimamura A; Ishikawa T; Fujiwara Y; Ichi I
[Ad] Endereço:Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
[Ti] Título:FADS2 inhibition in essential fatty acid deficiency induces hepatic lipid accumulation via impairment of very low-density lipoprotein (VLDL) secretion.
[So] Source:Biochem Biophys Res Commun;496(2):549-555, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Fatty acid desaturase 2 (FADS2) is responsible for the first desaturation reaction in the synthesis of highly unsaturated fatty acids (HUFAs), such as arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3), and is involved in Mead acid (20:3n-9) production during essential fatty acid deficiency (EFAD). In this study, an obvious hepatic lipid accumulation was observed in EFAD mice treated with a FADS2 inhibitor. FADS2 inhibition in the EFAD state reduced secretion of very low-density lipoprotein (VLDL) and markedly diminished Mead acid in phosphatidylcholine (PC) in the liver and plasma. As the results, the amount of C20 HUFAs in hepatic and plasma PC dramatically reduced in the EFAD mice treated with a FADS2 inhibitor, whereas the decrease of C20 HUFA levels of PC in EFAD mice was not observed because of the increased Mead acid in PC. These results supposed that Mead acid in PC is important as a component of VLDL. It is possible that Mead acid plays the role of a substitute of HUFAs in VLDL secretion during EFAD.
[Mh] Termos MeSH primário: Ácidos Graxos Dessaturases/metabolismo
Ácidos Graxos Insaturados/metabolismo
Lipoproteínas VLDL/metabolismo
Fígado/metabolismo
[Mh] Termos MeSH secundário: Ácido 8,11,14-Eicosatrienoico/análogos & derivados
Ácido 8,11,14-Eicosatrienoico/metabolismo
Animais
Ácidos Graxos Dessaturases/antagonistas & inibidores
Fígado Gorduroso/metabolismo
Metabolismo dos Lipídeos
Masculino
Camundongos Endogâmicos C57BL
Oxirredução
Fosfatidilcolinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fatty Acids, Unsaturated); 0 (Lipoproteins, VLDL); 0 (Phosphatidylcholines); 7324-41-6 (8,11,14-Eicosatrienoic Acid); EC 1.14.19.- (Fatty Acid Desaturases); EC 1.14.19.3 (FADS2 protein, mouse); JQS194YH3X (mead acid)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180122
[St] Status:MEDLINE


  2 / 1304 MEDLINE  
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[PMID]:29317615
[Au] Autor:An JU; Song YS; Kim KR; Ko YJ; Yoon DY; Oh DK
[Ad] Endereço:Department of Integrative Bioscience and Biotechnology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea.
[Ti] Título:Biotransformation of polyunsaturated fatty acids to bioactive hepoxilins and trioxilins by microbial enzymes.
[So] Source:Nat Commun;9(1):128, 2018 01 09.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Hepoxilins (HXs) and trioxilins (TrXs) are involved in physiological processes such as inflammation, insulin secretion and pain perception in human. They are metabolites of polyunsaturated fatty acids (PUFAs), including arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, formed by 12-lipoxygenase (LOX) and epoxide hydrolase (EH) expressed by mammalian cells. Here, we identify ten types of HXs and TrXs, produced by the prokaryote Myxococcus xanthus, of which six types are new, namely, HXB , HXD , HXE , TrXB , TrXD and TrXE . We succeed in the biotransformation of PUFAs into eight types of HXs (>35% conversion) and TrXs (>10% conversion) by expressing M. xanthus 12-LOX or 11-LOX with or without EH in Escherichia coli. We determine 11-hydroxy-eicosatetraenoic acid, HXB , HXB , HXD , TrXB and TrXD as potential peroxisome proliferator-activated receptor-γ partial agonists. These findings may facilitate physiological studies and drug development based on lipid mediators.
[Mh] Termos MeSH primário: Ácido 8,11,14-Eicosatrienoico/análogos & derivados
Ácidos Graxos Insaturados/metabolismo
Myxococcus xanthus/enzimologia
[Mh] Termos MeSH secundário: Ácido 8,11,14-Eicosatrienoico/química
Ácido 8,11,14-Eicosatrienoico/metabolismo
Araquidonato 12-Lipoxigenase/genética
Araquidonato 12-Lipoxigenase/metabolismo
Araquidonato Lipoxigenases/genética
Araquidonato Lipoxigenases/metabolismo
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Biotransformação
Epóxido Hidrolases/genética
Epóxido Hidrolases/metabolismo
Ácidos Graxos Insaturados/química
Redes e Vias Metabólicas/genética
Estrutura Molecular
Myxococcus xanthus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Fatty Acids, Unsaturated); 68860-46-8 (8,11,12-trihydroxy-5,9,14-eicosatrienoic acid); 7324-41-6 (8,11,14-Eicosatrienoic Acid); 85589-24-8 (8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid); EC 1.13.11.- (11-lipoxygenase); EC 1.13.11.- (Arachidonate Lipoxygenases); EC 1.13.11.31 (Arachidonate 12-Lipoxygenase); EC 3.3.2.- (Epoxide Hydrolases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02543-8


  3 / 1304 MEDLINE  
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[PMID]:28887431
[Au] Autor:Yonker LM; Pazos MA; Lanter BB; Mou H; Chu KK; Eaton AD; Bonventre JV; Tearney GJ; Rajagopal J; Hurley BP
[Ad] Endereço:Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114.
[Ti] Título:Neutrophil-Derived Cytosolic PLA2α Contributes to Bacterial-Induced Neutrophil Transepithelial Migration.
[So] Source:J Immunol;199(8):2873-2884, 2017 Oct 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Eicosanoids are a group of bioactive lipids that are shown to be important mediators of neutrophilic inflammation; selective targeting of their function confers therapeutic benefit in a number of diseases. Neutrophilic airway diseases, including cystic fibrosis, are characterized by excessive neutrophil infiltration into the airspace. Understanding the role of eicosanoids in this process may reveal novel therapeutic targets. The eicosanoid hepoxilin A3 is a pathogen-elicited epithelial-produced neutrophil chemoattractant that directs transepithelial migration in response to infection. Following hepoxilin A3-driven transepithelial migration, neutrophil chemotaxis is amplified through neutrophil production of a second eicosanoid, leukotriene B4 (LTB4). The rate-limiting step of eicosanoid generation is the liberation of arachidonic acid by phospholipase A2, and the cytosolic phospholipase A2 (cPLA2)α isoform has been specifically shown to direct LTB4 synthesis in certain contexts. Whether cPLA2α is directly responsible for neutrophil synthesis of LTB4 in the context of induced neutrophil transepithelial migration has not been explored. Human and mouse neutrophil epithelial cocultures were used to evaluate the role of neutrophil-derived cPLA2α in infection-induced transepithelial signaling by pharmacological and genetic approaches. Primary human airway basal stem cell derived epithelial cultures and micro-optical coherence tomography, a new imaging modality that captures two- and three-dimensional real-time dynamics of neutrophil transepithelial migration, were applied. Evidence from these studies suggests that cPLA2α expressed by neutrophils, but not epithelial cells, plays a significant role in infection-induced neutrophil transepithelial migration by mediating LTB4 synthesis during migration, which serves to amplify the magnitude of neutrophil recruitment in response to epithelial infection.
[Mh] Termos MeSH primário: Antígenos de Plaquetas Humanas/metabolismo
Fibrose Cística/imunologia
Neutrófilos/imunologia
Infecções por Pseudomonas/imunologia
Pseudomonas aeruginosa/imunologia
Mucosa Respiratória/imunologia
Migração Transendotelial e Transepitelial
[Mh] Termos MeSH secundário: Ácido 8,11,14-Eicosatrienoico/análogos & derivados
Ácido 8,11,14-Eicosatrienoico/metabolismo
Animais
Comunicação Celular
Linhagem Celular
Quimiotaxia
Técnicas de Cocultura
Citosol/metabolismo
Seres Humanos
Leucotrieno B4/metabolismo
Camundongos
Neutrófilos/microbiologia
Mucosa Respiratória/microbiologia
Mucosa Respiratória/patologia
Tomografia de Coerência Óptica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Human Platelet); 0 (human platelet antigen 1b); 1HGW4DR56D (Leukotriene B4); 7324-41-6 (8,11,14-Eicosatrienoic Acid); 85589-24-8 (8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170910
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700539


  4 / 1304 MEDLINE  
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[PMID]:28587983
[Au] Autor:Huang X; Wang Y; Zhang Z; Wang Y; Chen X; Wang Y; Gao Y
[Ad] Endereço:Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
[Ti] Título:Ophiopogonin D and EETs ameliorate Ang II-induced inflammatory responses via activating PPARα in HUVECs.
[So] Source:Biochem Biophys Res Commun;490(2):123-133, 2017 Aug 19.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CYP2J2 is highly expressed in cardiovascular tissue including the heart and vascular endothelial cells. CYP2J2 and the EETs have been shown owning diverse biological effects. Our previous study found that ophiopogonin D (OP-D) suppressed drug-induced endoplasmic reticulum (ER) stress by upregulating the levels of CYP2J3/EETs in cardiomyocytes. The aim of this research was to investigate whether CYP2J2/EETs-PPARα pathway involved in endothelium protective effects of OP-D in human umbilical vein endothelial cells (HUVECs). The results showed that OP-D significantly inhibited Ang II induced NF-κB nuclear translocation, IκBα down-regulation and activation of pro-inflammatory cytokines (TNF-α, IL-6 and VCAM-1) by increasing the expression of CYP2J2/EETs and PPARα in HUVECs. Furthermore, treatment with exogenous 11,12-EET attenuated endothelial inflammation induced by Ang II as evidenced by inhibited NF-κB nuclear translocation, increased IκBα expression and decreased inflammation factor level. Finally, the activation of NF-κB nuclear translocation induced by Ang II was also markedly suppressed by fenofibrate. Co-incubation with 6-(2-proparglyloxyphenyl) hexanoic acid (PPOH) and PPARα inhibitor GW6471 before drug treatment abolished the endothelium protective effects of OP-D. Taken together, these data suggest that OP-D has the endothelial protective effect through activation of CYP2J and increasing EETs, and PPARα involves in this process.
[Mh] Termos MeSH primário: Ácido 8,11,14-Eicosatrienoico/farmacologia
Angiotensina II/farmacologia
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Inflamação/tratamento farmacológico
PPAR alfa/metabolismo
Saponinas/farmacologia
Espirostanos/farmacologia
[Mh] Termos MeSH secundário: Ácido 8,11,14-Eicosatrienoico/análogos & derivados
Células Cultivadas
Células Endoteliais da Veia Umbilical Humana/metabolismo
Seres Humanos
Inflamação/induzido quimicamente
Inflamação/metabolismo
NF-kappa B/metabolismo
Transporte Proteico/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NF-kappa B); 0 (PPAR alpha); 0 (Saponins); 0 (Spirostans); 11128-99-7 (Angiotensin II); 41753-55-3 (ophiopogonin D); 7324-41-6 (8,11,14-Eicosatrienoic Acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170608
[St] Status:MEDLINE


  5 / 1304 MEDLINE  
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[PMID]:28490483
[Au] Autor:Lei S; Huang F; Zhao A; Chen T; Chen W; Xie G; Zheng X; Zhang Y; Yu H; Zhang P; Rajani C; Bao Y; Jia W; Jia W
[Ad] Endereço:Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
[Ti] Título:The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity.
[So] Source:FASEB J;31(9):3904-3912, 2017 Sep.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bile acid (BA) signaling regulates fatty acid metabolism. BA dysregulation plays an important role in the development of metabolic disease. However, BAs in relation to fatty acids have not been fully investigated in obesity-related metabolic disorders. A targeted metabolomic measurement of serum BA and free fatty acid profiles was applied to sera of 381 individuals in 2 independent studies. The results showed that the ratio of dihomo-γ-linolenic acid (DGLA) to deoxycholic acid (DCA) species (DCAS) was significantly increased in obese individuals with type 2 diabetes (T2DM) from a case-control study and decreased in the remission group of obese subjects with T2DM after metabolic surgery. The changes were closely associated with their metabolic status. These results were consistently confirmed in both serum and liver of mice with diet-induced obesity, implying that such a metabolic alteration in circulation reflects changes occurring in the liver. studies of human liver L-02 cell lines under BA treatment revealed that DCA and its conjugated form, TDCA, significantly inhibited mRNA expression of fatty acid transport protein 5 in the presence of DGLA, which was involved in hepatocyte DGLA uptake. Thus, the DGLA:DCAS ratio may be a promising biomarker for metabolic abnormalities in obesity.-Lei, S., Huang, F., Zhao, A., Chen, T., Chen, W., Xie, G., Zheng, X., Zhang, Y., Yu, H., Zhang, P., Rajani, C., Bao, Y., Jia, W., Jia, W. The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity.
[Mh] Termos MeSH primário: Ácido 8,11,14-Eicosatrienoico/metabolismo
Ácido Desoxicólico/metabolismo
Obesidade/sangue
[Mh] Termos MeSH secundário: Adulto
Animais
Biomarcadores
Linhagem Celular
Ácido Desoxicólico/química
Dieta Hiperlipídica/efeitos adversos
Feminino
Teste de Tolerância a Glucose
Hepatócitos/metabolismo
Seres Humanos
Resistência à Insulina
Masculino
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 005990WHZZ (Deoxycholic Acid); 7324-41-6 (8,11,14-Eicosatrienoic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170512
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201700055R


  6 / 1304 MEDLINE  
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[PMID]:28332266
[Au] Autor:Bihzad SM; Yousif MH
[Ad] Endereço:Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
[Ti] Título:11,12-Epoxyeicosatrienoic acid induces vasodilator response in the rat perfused mesenteric vasculature.
[So] Source:Auton Autacoid Pharmacol;37(1):3-12, 2017 Jan.
[Is] ISSN:1474-8673
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Epoxyeicosatrienoic acids (EETs) are endogenous ligands that undergo hydrolysis by soluble epoxide hydrolase (sEH). The responses of 11, 12-EET in comparison with other vasodilator agonists including carbachol and sodium nitroprusside (SNP) were investigated. The effect of 1-cyclohexyl-3-dodecyl urea (CDU), a sEH, was tested on the vasodilator effect induced by 11, 12-EET in the perfused mesenteric beds isolated from normo-glycaemic and type-1 STZ-diabetic rats. In the perfused mesenteric beds of control and diabetic animals, 11, 12-EET produced vasodilation in a dose-dependent manner. The vasodilator response induced by 11, 12-EET was significantly decreased in tissues obtained from diabetic animals, but this was significantly corrected through inhibition of sEH. The effects of nitric oxide synthase inhibitor, cyclo-oxygenase inhibitor, specific potassium channel inhibitors, soluble guanylyl cyclase inhibitor and transient receptor potential channel V4 inhibitor, on vasodilator response to 11, 12-EET were investigated. In tissues isolated from control animals, vasodilator responses to 11, 12-EET were not inhibited by acute incubation with l-NAME, l-NAME with indomethacin, glibenclamide, iberiotoxin, charybdotoxin, apamin or ODQ. Incubation with the transient receptor potential channel V4 inhibitor ruthenium red caused significantly reduced vasodilator responses induced by 11, 12-EET. In conclusion, results from this study indicate that 11, 12-EET has a vasodilator effect in the perfused mesenteric bed, partly through activation of vanilloid receptor. A strategy to elevate the levels of EETs may have a significant impact in correcting microvascular abnormality associated with diabetes.
[Mh] Termos MeSH primário: Ácido 8,11,14-Eicosatrienoico/análogos & derivados
Circulação Esplâncnica/efeitos dos fármacos
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: Ácido 8,11,14-Eicosatrienoico/farmacologia
Animais
Inibidores de Ciclo-Oxigenase/farmacologia
Diabetes Mellitus Experimental/fisiopatologia
Relação Dose-Resposta a Droga
Interações Medicamentosas
Inibidores Enzimáticos/farmacologia
Guanilato Ciclase/antagonistas & inibidores
Masculino
Óxido Nítrico Sintase/antagonistas & inibidores
Perfusão
Bloqueadores dos Canais de Potássio/farmacologia
Ratos
Ratos Sprague-Dawley
Canais de Receptores Transientes de Potencial/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclooxygenase Inhibitors); 0 (Enzyme Inhibitors); 0 (Potassium Channel Blockers); 0 (Transient Receptor Potential Channels); 0 (Vasodilator Agents); 5DOQ38R4UW (11,12-epoxy-5,8,14-eicosatrienoic acid); 7324-41-6 (8,11,14-Eicosatrienoic Acid); EC 1.14.13.39 (Nitric Oxide Synthase); EC 4.6.1.2 (Guanylate Cyclase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1111/aap.12052


  7 / 1304 MEDLINE  
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[PMID]:28319086
[Au] Autor:Zhao H; Chen J; Chai J; Zhang Y; Yu C; Pan Z; Gao P; Zong C; Guan Q; Fu Y; Liu Y
[Ad] Endereço:Department of Endocrinology, Qingdao Municipal Hospital, Qingdao, China.
[Ti] Título:Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing.
[So] Source:Lab Invest;97(7):782-791, 2017 Jul.
[Is] ISSN:1530-0307
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In the present study, we aimed to explore the role and effects of CYP epoxygenases/EETs in wound healing in ob/ob mice. Full-thickness skin dorsal wounds were made on ob/ob mice and C57BL/6 control mice. The mRNA and protein expression of CYP epoxygenases were determined in granulation tissues of wounds. Effects of EETs on wound healing were evaluated. Inflammation and angiogenesis in wounds were also observed. Compared with C57BL/6 mice, the mRNA and protein expression of CYP2C65 and CYP2J6 in the granulation tissues in ob/ob mice were significantly reduced. 11,12-EET treatment significantly improved wound healing in ob/ob mice, whereas 14,15-EEZE, an EET antagonist, showed the opposite effect. 11,12-EET treatment decreased neutrophil and macrophage infiltration to the wound sites, resulting in reduced production of inflammatory cytokines, decreased MMP-9 expression, and increased collagen accumulation in the granulation tissues of ob/ob mice. In addition, 11,12-EET increased angiogenesis in the granulation tissues of wounds in ob/ob mice. These findings indicate that reduced expression of CYP epoxygenases may contribute to impaired diabetic wound healing, and exogenous EETs may improve diabetic wound healing by modulating inflammation and angiogenesis.
[Mh] Termos MeSH primário: Ácido 8,11,14-Eicosatrienoico/análogos & derivados
Sistema Enzimático do Citocromo P-450/efeitos dos fármacos
Sistema Enzimático do Citocromo P-450/metabolismo
Complicações do Diabetes/metabolismo
Úlcera Cutânea/metabolismo
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Ácido 8,11,14-Eicosatrienoico/farmacologia
Animais
Sistema Enzimático do Citocromo P-450/genética
Citocinas/análise
Citocinas/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Obesos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (14,15-eicosa-5-enoic acid); 0 (Cytokines); 5DOQ38R4UW (11,12-epoxy-5,8,14-eicosatrienoic acid); 7324-41-6 (8,11,14-Eicosatrienoic Acid); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.14.14.1 (arachidonate epoxygenase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170321
[St] Status:MEDLINE
[do] DOI:10.1038/labinvest.2017.21


  8 / 1304 MEDLINE  
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[PMID]:28235735
[Au] Autor:Yary T; Tolmunen T; Lehto SM; Tuomainen TP; Nurmi T; Kauhanen J; Voutilainen S; Ruusunen A
[Ad] Endereço:University of Eastern Finland, Institute of Public Health and Clinical Nutrition, P.O. Box 1627, 70211 Kuopio, Finland.
[Ti] Título:Serum dihomo-γ-linolenic acid level is inversely associated with the risk of depression. A 21-year follow-up study in general population men.
[So] Source:J Affect Disord;213:151-155, 2017 Apr 15.
[Is] ISSN:1573-2517
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Depression is a major public health challenge worldwide, and polyunsaturated fatty acids (PUFAs), especially n-3 PUFAs, have been found to inversely associate with the risk of depression. However, only few cross-sectional studies have investigated the association between dihomo-γ-linolenic acid (DGLA), an n-6 PUFA with anti-inflammatory effects, and depression. The aims of the present study were to examine an association between serum DGLA and the risk of depression, and to study whether the potential association is mediated via inflammation. METHODS: A 20-year prospective Kuopio Ischaemic Heart Disease Risk Factor (KIHD) follow-up study was conducted from 1984 to 1989 with 2179 middle-aged and older Finnish men (42-60 years old at baseline). The baseline concentrations of serum fatty acids, including DGLA, were determined. A hospital discharge diagnosis of depression was used as the main outcome and obtained from linkage to National Hospital Discharge Register. Serum C-reactive protein (CRP) levels were measured to assess inflammation. RESULTS: An inverse association between serum DGLA concentration and incidence of depression was found after adjustment for several potential confounders (Hazard ratio HR 0.53, CI 0.36-0.79, P=0.002). The association between DGLA and depression was not dependent on inflammation (P-interaction=0.618). LIMITATIONS: Our findings may not be generalizable to individuals below middle-age or women. Moreover, we were unable to consider cases with mild depression in the longitudinal setting. CONCLUSIONS: Higher serum DGLA concentrations may predict lower risk of develop depression in elderly men. Further studies are warranted to address potential mechanisms as mechanism behind this association remains unclear.
[Mh] Termos MeSH primário: Ácido 8,11,14-Eicosatrienoico/sangue
Depressão/sangue
Depressão/epidemiologia
[Mh] Termos MeSH secundário: Adulto
Proteína C-Reativa/metabolismo
Finlândia/epidemiologia
Seguimentos
Seres Humanos
Incidência
Inflamação
Masculino
Meia-Idade
Estudos Prospectivos
Soro/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
7324-41-6 (8,11,14-Eicosatrienoic Acid); 9007-41-4 (C-Reactive Protein)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170226
[St] Status:MEDLINE


  9 / 1304 MEDLINE  
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[PMID]:27884766
[Au] Autor:Yang L; Cheriyan J; Gutterman DD; Mayer RJ; Ament Z; Griffin JL; Lazaar AL; Newby DE; Tal-Singer R; Wilkinson IB
[Ad] Endereço:Experimental Medicine and Immunotherapeutics (EMIT), University of Cambridge, Addenbrooke's Hospital, Cambridge, England.
[Ti] Título:Mechanisms of Vascular Dysfunction in COPD and Effects of a Novel Soluble Epoxide Hydrolase Inhibitor in Smokers.
[So] Source:Chest;151(3):555-563, 2017 Mar.
[Is] ISSN:1931-3543
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Smoking and COPD are risk factors for cardiovascular disease, and the pathogenesis may involve endothelial dysfunction. We tested the hypothesis that endothelium-derived epoxyeicosatrienoic acid (EET)-mediated endothelial function is impaired in patients with COPD and that a novel soluble epoxide hydrolase inhibitor, GSK2256294, attenuates EET-mediated endothelial dysfunction in human resistance vessels both in vitro and in vivo. METHODS: Endogenous and stimulated endothelial release of EETs was assessed in 12 patients with COPD, 11 overweight smokers, and two matched control groups, using forearm plethysmography with intraarterial infusions of fluconazole, bradykinin, and the combination. The effects of GSK2256294 on EET-mediated vasodilation in human resistance arteries were assessed in vitro and in vivo in a phase I clinical trial in healthy overweight smokers. RESULTS: Compared with control groups, there was reduced vasodilation with bradykinin (P = .005), a blunted effect of fluconazole on bradykinin-induced vasodilation (P = .03), and a trend toward reduced basal EET/dihydroxyepoxyeicosatrienoic acid ratio in patients with COPD (P = .08). A similar pattern was observed in overweight smokers. In vitro, 10 µM GSK2256294 increased 11,12-EET-mediated vasodilation compared with vehicle (90% ± 4.2% vs 72.6% ± 6.2% maximal dilatation) and shifted the bradykinin half-maximal effective concentration (EC50) (-8.33 ± 0.172 logM vs -8.10 ± 0.118 logM; P = .001 for EC50). In vivo, 18 mg GSK2256294 improved the maximum bradykinin response from 338% ± 46% before a dose to 566% ± 110% after a single dose (P = .02) and to 503% ± 123% after a chronic dose (P = .003). CONCLUSIONS: GSK2256294 attenuates smoking-related EET-mediated endothelial dysfunction, suggesting potential therapeutic benefits in patients with COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01762774; URL: www.clinicaltrials.gov.
[Mh] Termos MeSH primário: Vasos Sanguíneos/efeitos dos fármacos
Cicloexilaminas/farmacologia
Endotélio Vascular/efeitos dos fármacos
Epóxido Hidrolases/antagonistas & inibidores
Sobrepeso/fisiopatologia
Doença Pulmonar Obstrutiva Crônica/fisiopatologia
Fumar/fisiopatologia
Triazinas/farmacologia
Vasodilatação/efeitos dos fármacos
[Mh] Termos MeSH secundário: Ácido 8,11,14-Eicosatrienoico/análogos & derivados
Ácido 8,11,14-Eicosatrienoico/metabolismo
Adulto
Idoso
Vasos Sanguíneos/fisiopatologia
Bradicinina/farmacologia
Estudos de Casos e Controles
Endotélio Vascular/metabolismo
Endotélio Vascular/fisiopatologia
Fluconazol/farmacologia
Antebraço/irrigação sanguínea
Seres Humanos
Técnicas In Vitro
Masculino
Meia-Idade
Sobrepeso/metabolismo
Pletismografia
Doença Pulmonar Obstrutiva Crônica/metabolismo
Fumar/metabolismo
Vasodilatadores/farmacologia
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclohexylamines); 0 (N-((4-cyano-2-(trifluoromethyl)phenyl)methyl)-3-((4-methyl-6-(methylamino)-1,3,5-triazin-2-yl)amino)cyclohexanecarboxamide); 0 (Triazines); 0 (Vasodilator Agents); 5DOQ38R4UW (11,12-epoxy-5,8,14-eicosatrienoic acid); 7324-41-6 (8,11,14-Eicosatrienoic Acid); 8VZV102JFY (Fluconazole); EC 3.3.2.- (Epoxide Hydrolases); S8TIM42R2W (Bradykinin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161126
[St] Status:MEDLINE


  10 / 1304 MEDLINE  
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[PMID]:27782740
[Au] Autor:Sporková A; Husková Z; Skaroupková P; Rami Reddy N; Falck JR; Sadowski J; Cervenka L
[Ad] Endereço:Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Pathophysiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. luce@medicon.cz.
[Ti] Título:Vasodilatory responses of renal interlobular arteries to epoxyeicosatrienoic acids analog are not enhanced in Ren-2 transgenic hypertensive rats: evidence against a role of direct vascular effects of epoxyeicosatrienoic acids in progression of experimental heart failure.
[So] Source:Physiol Res;66(1):29-39, 2017 Mar 31.
[Is] ISSN:1802-9973
[Cp] País de publicação:Czech Republic
[La] Idioma:eng
[Ab] Resumo:Pathophysiological mechanisms underlying the development of renal dysfunction and progression of congestive heart failure (CHF) remain poorly understood. Recent studies have revealed striking differences in the role of epoxyeicosatrienoic acids (EETs), active products of cytochrome P-450-dependent epoxygenase pathway of arachidonic acid, in the progression of aorto-caval fistula (ACF)-induced CHF between hypertensive Ren-2 renin transgenic rats (TGR) and transgene-negative normotensive Hannover Sprague-Dawley (HanSD) controls. Both ACF TGR and ACF HanSD strains exhibited marked intrarenal EETs deficiency and impairment of renal function, and in both strains chronic pharmacologic inhibition of soluble epoxide hydrolase (sEH) (which normally degrades EETs) normalized EETs levels. However, the treatment improved the survival rate and attenuated renal function impairment in ACF TGR only. Here we aimed to establish if the reported improved renal function and attenuation of progression of CHF in ACF TGR observed after she blockade depends on increased vasodilatory responsiveness of renal resistance arteries to EETs. Therefore, we examined the responses of interlobar arteries from kidneys of ACF TGR and ACF HanSD rats to EET-A, a new stable 14,15-EET analog. We found that the arteries from ACF HanSD kidneys rats exhibited greater vasodilator responses when compared to the ACF TGR arteries. Hence, reduced renal vasodilatory responsiveness cannot be responsible for the lack of beneficial effects of chronic sEH inhibition on the development of renal dysfunction and progression of CHF in ACF HanSD rats.
[Mh] Termos MeSH primário: Ácido 8,11,14-Eicosatrienoico/análogos & derivados
Insuficiência Cardíaca/fisiopatologia
Hipertensão/fisiopatologia
Rim/irrigação sanguínea
Renina/fisiologia
Vasodilatação/fisiologia
[Mh] Termos MeSH secundário: Ácido 8,11,14-Eicosatrienoico/química
Ácido 8,11,14-Eicosatrienoico/farmacologia
Acetilcolina/farmacologia
Animais
Progressão da Doença
Relação Dose-Resposta a Droga
Insuficiência Cardíaca/genética
Hipertensão/genética
Rim/efeitos dos fármacos
Rim/fisiologia
Masculino
Norepinefrina/farmacologia
Ratos
Ratos Sprague-Dawley
Ratos Transgênicos
Circulação Renal/efeitos dos fármacos
Circulação Renal/fisiologia
Vasodilatação/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ren2 protein, rat); 7324-41-6 (8,11,14-Eicosatrienoic Acid); 81276-03-1 (14,15-epoxy-5,8,11-eicosatrienoic acid); EC 3.4.23.15 (Renin); N9YNS0M02X (Acetylcholine); X4W3ENH1CV (Norepinephrine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161027
[St] Status:MEDLINE



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