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[PMID]:29327928
[Au] Autor:Zhu ZJ; Chen HM; Chen JJ; Yang R; Yan XJ
[Ad] Endereço:Key Laboratory of Marine Biotechnology of Zhejiang Province, Ningbo University , Ningbo, Zhejiang 315211, China.
[Ti] Título:One-Step Bioconversion of Fatty Acids into C8-C9 Volatile Aroma Compounds by a Multifunctional Lipoxygenase Cloned from Pyropia haitanensis.
[So] Source:J Agric Food Chem;66(5):1233-1241, 2018 Feb 07.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The multifunctional lipoxygenase PhLOX cloned from Pyropia haitanensis was expressed in Escherichia coli with 24.4 mg·L yield. PhLOX could catalyze the one-step bioconversion of C18-C22 fatty acids into C8-C9 volatile organic compounds (VOCs), displaying higher catalytic efficiency for eicosenoic and docosenoic acids than for octadecenoic acids. C20:5 was the most suitable substrate among the tested fatty acids. The C8-C9 VOCs were generated in good yields from fatty acids, e.g., 2E-nonenal from C20:4, and 2E,6Z-nonadienal from C20:5. Hydrolyzed oils were also tested as substrates. The reactions mainly generated 2E,4E-pentadienal, 2E-octenal, and 2E,4E-octadienal from hydrolyzed sunflower seed oil, corn oil, and fish oil, respectively. PhLOX showed good stability after storage at 4 °C for 2 weeks and broad tolerance to pH and temperature. These desirable properties of PhLOX make it a promising novel biocatalyst for the industrial production of volatile aroma compounds.
[Mh] Termos MeSH primário: Ácidos Graxos/metabolismo
Lipoxigenase/genética
Lipoxigenase/metabolismo
Proteínas Recombinantes/metabolismo
Rodófitas/enzimologia
Compostos Orgânicos Voláteis/metabolismo
[Mh] Termos MeSH secundário: Clonagem Molecular
Óleo de Milho/metabolismo
Estabilidade Enzimática
Ácidos Erúcicos/metabolismo
Escherichia coli/genética
Ácidos Graxos Monoinsaturados/metabolismo
Óleos de Peixe/metabolismo
Expressão Gênica
Concentração de Íons de Hidrogênio
Rodófitas/genética
Especificidade por Substrato
Óleo de Girassol/metabolismo
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Erucic Acids); 0 (Fatty Acids); 0 (Fatty Acids, Monounsaturated); 0 (Fish Oils); 0 (Recombinant Proteins); 0 (Sunflower Oil); 0 (Volatile Organic Compounds); 8001-30-7 (Corn Oil); EC 1.13.11.12 (Lipoxygenase); UDX6WPL94T (eicosenoic acid)
[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:180113
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b05341


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[PMID]:29363364
[Au] Autor:Vlainic J; Kosalec I; Pavic K; Hadjipavlou-Litina D; Pontiki E; Zorc B
[Ad] Endereço:a Laboratory for Advanced Genomics, Division of Molecular Medicine , Rudjer Boskovic Institute , Zagreb , Croatia.
[Ti] Título:Insights into biological activity of ureidoamides with primaquine and amino acid moieties.
[So] Source:J Enzyme Inhib Med Chem;33(1):376-382, 2018 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Primaquine (PQ) ureidoamides 5a-f were screened for antimicrobial, biofilm eradication and antioxidative activities. Susceptibility of the tested microbial species towards tested compounds showed species- and compound-dependent activity. N-(diphenylmethyl)-2-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]-4-methylpentanamide (5a) and 2-(4-chlorophenyl)-N-(diphenylmethyl)-2-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]acetamide (5d) showed antibacterial activity against S. aureus strains (MIC = 6.5 µg/ml). Further, compounds 5c and 5d had weak antibacterial activity against Escherichia coli and Pseudomonas aeruginosa. None of the tested compounds showed a wide spectrum of antifungal activity. In contrast, most of the compounds exerted strong activity in a biofilm eradication assay against E. coli, P. aeruginosa and Candida albicans, comparable to or even higher than gentamycin, amphotericin B or parent PQ. The most active compounds were 5a and 5b. Tested compounds were inactive against biofilm formation by C. parapsylosis, Enterococcus faecalis, C. tropicalis and C. krusei. Compounds 5b-f significantly inhibited lipid peroxidation (80-99%), whereas compound 5c presented interesting LOX inhibition.
[Mh] Termos MeSH primário: Amidas/farmacologia
Aminoácidos/farmacologia
Antibacterianos/farmacologia
Antifúngicos/farmacologia
Antioxidantes/farmacologia
Primaquina/farmacologia
[Mh] Termos MeSH secundário: Amidas/química
Aminoácidos/química
Antibacterianos/química
Antifúngicos/química
Antioxidantes/química
Biofilmes/efeitos dos fármacos
Candida albicans/efeitos dos fármacos
Relação Dose-Resposta a Droga
Escherichia coli/efeitos dos fármacos
Seres Humanos
Peroxidação de Lipídeos/efeitos dos fármacos
Lipoxigenase/metabolismo
Inibidores de Lipoxigenase/química
Inibidores de Lipoxigenase/farmacologia
Testes de Sensibilidade Microbiana
Estrutura Molecular
Primaquina/química
Pseudomonas aeruginosa/efeitos dos fármacos
Feijão de Soja/enzimologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Amino Acids); 0 (Anti-Bacterial Agents); 0 (Antifungal Agents); 0 (Antioxidants); 0 (Lipoxygenase Inhibitors); EC 1.13.11.12 (Lipoxygenase); MVR3634GX1 (Primaquine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1423067


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[PMID]:29235601
[Au] Autor:Mandal P; Kundu BK; Vyas K; Sabu V; Helen A; Dhankhar SS; Nagaraja CM; Bhattacherjee D; Bhabak KP; Mukhopadhyay S
[Ad] Endereço:Department of Chemistry, School of Basic Sciences, Indian Institute of Technology Indore, Indore 453552, India. suman@iiti.ac.in.
[Ti] Título:Ruthenium(ii) arene NSAID complexes: inhibition of cyclooxygenase and antiproliferative activity against cancer cell lines.
[So] Source:Dalton Trans;47(2):517-527, 2018 Jan 02.
[Is] ISSN:1477-9234
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of molecules which have been found to be active against cancer cells with chemopreventive properties by targeting cyclooxygenase (COX-1 and COX-2) and lipoxygenase (LOX), commonly upregulated (particularly COX-2) in malignant tumors. Arene ruthenium(ii) complexes with a pseudo-octahedral coordination environment containing different ancillary ligands have shown remarkable activity against primary and metastatic tumors as reported earlier. This work describes the synthesis of four novel ruthenium(ii)-arene complexes viz. [Ru(η -p-cymene)(nap)Cl] 1 [Hnap = naproxen or (S)-2-(6-methoxy-2-naphthyl)propionic acid], [Ru(η -p-cymene)(diclo)Cl] 2 [Hdiclo = diclofenac or 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, [Ru(η -p-cymene)(ibu)Cl] 3 [Hibu = ibuprofen or 2-(4-isobutylphenyl)propanoic acid] and [Ru(η -p-cymene)(asp)Cl] 4 [Hasp = aspirin or 2-acetoxy benzoic acid] using different NSAIDs as chelating ligands. Complexes 1-3 have shown promising antiproliferative activity against three different cell lines with GI (concentration of drug causing 50% inhibition of cell growth) values comparable to adriamycin. At the concentration of 50 µM, complex 3 is more effective in the inhibition of cyclooxygenase and lipooxygenase enzymes, followed by complex 2 and complex 1 in comparison to their respective free NSAID ligands indicating a possible correlation between the inhibition of COX and/or LOX and anticancer properties. Molecular docking studies with COX-2 reveal that complexes 1 and 2 having naproxen and diclofenac ligands exhibit stronger interactions with COX-2 than their respective free NSAIDs and these results are in good agreement with their relative experimentally observed COX inhibition as well as anti-proliferative activities.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/química
Benzeno/química
Compostos Organometálicos/química
Compostos Organometálicos/farmacologia
Prostaglandina-Endoperóxido Sintases/metabolismo
Rutênio/química
[Mh] Termos MeSH secundário: Animais
Bovinos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Ciclo-Oxigenase 1/química
Ciclo-Oxigenase 1/metabolismo
Ciclo-Oxigenase 2/química
Ciclo-Oxigenase 2/metabolismo
Inibidores de Ciclo-Oxigenase/síntese química
Inibidores de Ciclo-Oxigenase/química
Inibidores de Ciclo-Oxigenase/metabolismo
Inibidores de Ciclo-Oxigenase/farmacologia
DNA/metabolismo
Dimetil Sulfóxido/química
Estabilidade de Medicamentos
Seres Humanos
Lipoxigenase/metabolismo
Inibidores de Lipoxigenase/síntese química
Inibidores de Lipoxigenase/química
Inibidores de Lipoxigenase/metabolismo
Inibidores de Lipoxigenase/farmacologia
Simulação de Acoplamento Molecular
Compostos Organometálicos/síntese química
Compostos Organometálicos/metabolismo
Prostaglandina-Endoperóxido Sintases/química
Conformação Proteica
Soroalbumina Bovina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Cyclooxygenase Inhibitors); 0 (Lipoxygenase Inhibitors); 0 (Organometallic Compounds); 27432CM55Q (Serum Albumin, Bovine); 7UI0TKC3U5 (Ruthenium); 9007-49-2 (DNA); EC 1.13.11.12 (Lipoxygenase); EC 1.14.99.1 (Cyclooxygenase 1); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases); J64922108F (Benzene); YOW8V9698H (Dimethyl Sulfoxide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1039/c7dt03637j


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[PMID]:29235833
[Au] Autor:Molodchenkova OO; Adamovskaya VG; Ciselskaya LY; Bezkrovnaya LY; Kartuzova TV; Iablonska VB
[Ti] Título:Purification and properties of lipoxygenase from wheat seedlings infected by Fusarium graminearum and treated by salicylic acid.
[So] Source:Ukr Biochem J;88(6):26-34, 2016 Nov-Dec.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:Lipoxygenase from wheat seedlings in normal conditions, infected by Fusarium graminearum and treated by salicylic acid was isolated. The isolated enzyme was purified by the methods of salting-out (60% ammonium sulphate), dialysis, gel-filtration and ion-exchange chromatography. Specific activity of the purified enzyme was 8.0-12.5 ΔЕ234/mg of protein, degree of purification ­ 11.6-15.3 times. The enzyme yield was 18.3-27.9%. Molecular mass of lipoxygenase is 90 kDa, amino acid composition is distinguished by a high content of glutamic acid, proline, valine, isoleucine, leucine and low level of histidine, tyrosine, phenylalanine, threonine, tryptophan, cystein. Research of lipoxygenase substrate dependence indicated that the enzyme catalysed with the maximum velocity of the reaction of arachidonic acid oxidation at a substrate concentration of 4.5 mM at pH 7.2, the reaction of linoleic acid oxidation at a substrate concentration of 4.5 mM at pH 7.2 and the reaction of linolenic acid oxidation at a substrate concentration of 9.0 mM at pH 8.0. The change of wheat lipoxygenase activity depending on genotype resistance to Fusarium graminearum and millieu of germination was shown. One of the manifestations of the protective effect of salicylic acid is its ability to induce changes of lipoxygenase activity.
[Mh] Termos MeSH primário: Fungicidas Industriais/farmacologia
Lipoxigenase/isolamento & purificação
Proteínas de Plantas/isolamento & purificação
Ácido Salicílico/farmacologia
Triticum/efeitos dos fármacos
[Mh] Termos MeSH secundário: Aminoácidos/química
Ácido Araquidônico/metabolismo
Cromatografia por Troca Iônica
Resistência à Doença
Suscetibilidade a Doenças/enzimologia
Suscetibilidade a Doenças/imunologia
Fusarium/efeitos dos fármacos
Fusarium/crescimento & desenvolvimento
Fusarium/patogenicidade
Expressão Gênica
Concentração de Íons de Hidrogênio
Cinética
Ácido Linoleico/metabolismo
Lipoxigenase/metabolismo
Peso Molecular
Doenças das Plantas/imunologia
Doenças das Plantas/microbiologia
Doenças das Plantas/prevenção & controle
Proteínas de Plantas/metabolismo
Plântulas/efeitos dos fármacos
Plântulas/enzimologia
Plântulas/imunologia
Plântulas/microbiologia
Especificidade por Substrato
Triticum/enzimologia
Triticum/imunologia
Triticum/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Fungicides, Industrial); 0 (Plant Proteins); 27YG812J1I (Arachidonic Acid); 9KJL21T0QJ (Linoleic Acid); EC 1.13.11.12 (Lipoxygenase); O414PZ4LPZ (Salicylic Acid)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.06.026


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[PMID]:28465089
[Au] Autor:Zahradka P; Neumann S; Aukema HM; Taylor CG
[Ad] Endereço:Department of Physiology and Pathophysiology, University of Manitoba, Canada; Department of Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Albrechtsen Research Centre, Winnipeg, Canada. Electronic address: pzahr
[Ti] Título:Adipocyte lipid storage and adipokine production are modulated by lipoxygenase-derived oxylipins generated from 18-carbon fatty acids.
[So] Source:Int J Biochem Cell Biol;88:23-30, 2017 07.
[Is] ISSN:1878-5875
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Generation of oxylipins (oxygenated metabolites of fatty acids) by lipoxygenases may be responsible for the beneficial effects of 20- and 22-carbon n-3 fatty acids on adipose tissue dysfunction in obesity, but the potential actions of oxylipins derived from 18-carbon fatty acids, which are generally at higher levels in the diet, are unknown. We therefore compared the effects of select lipoxygenase-derived oxylipins produced from α-linolenic acid (ALA, C18:3 n-3), linoleic acid (LA, C18:2 n-6), and arachidonic acid (AA, C20:4 n-6) on key adipocyte functions that are altered in obesity. Individual oxylipins were added to the culture medium of differentiating 3T3-L1 preadipocytes for 6days. Lipid accumulation was subsequently determined by Oil Red O staining, while Western blotting was used to measure levels of proteins associated with lipid metabolism and characteristics of adipocyte functionality. Addition of all oxylipins at 30nM was sufficient to significantly decrease triglyceride accumulation in lipid droplets, and higher levels completely blocked lipid production. Our results establish that lipoxygenase-derived oxylipins produced from 18-carbon PUFA differentially affect multiple adipocyte processes associated with lipid storage and adipokine production. However, these effects are not due to the oxylipins blocking adipocyte maturation and thus globally suppressing all adipocyte characteristics. Furthermore, these oxylipin species decrease the lipid content of adipocytes regardless from which precursor fatty acid or lipoxygenase they were derived. Consequently, adipocyte characteristics can be altered through the ability of oxylipins to selectively modulate levels of proteins involved in both lipid metabolism and adipokine production.
[Mh] Termos MeSH primário: Adipócitos/efeitos dos fármacos
Adipócitos/metabolismo
Adipocinas/biossíntese
Gotículas Lipídicas/efeitos dos fármacos
Lipoxigenase/metabolismo
Oxilipinas/metabolismo
Oxilipinas/farmacologia
[Mh] Termos MeSH secundário: Células 3T3-L1
Adipócitos/citologia
Animais
Diferenciação Celular/efeitos dos fármacos
Gotículas Lipídicas/metabolismo
Camundongos
Oxilipinas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adipokines); 0 (Oxylipins); EC 1.13.11.12 (Lipoxygenase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


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[PMID]:29207281
[Au] Autor:Mazur R; Trzcinska-Danielewicz J; Kozlowski P; Kowalewska L; Rumak I; Shiell BJ; Mostowska A; Michalski WP; Garstka M
[Ad] Endereço:Department of Metabolic Regulation, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland. Electronic address: rmazur@biol.uw.edu.pl.
[Ti] Título:Dark-chilling and subsequent photo-activation modulate expression and induce reversible association of chloroplast lipoxygenase with thylakoid membrane in runner bean (Phaseolus coccineus L.).
[So] Source:Plant Physiol Biochem;122:102-112, 2018 Jan.
[Is] ISSN:1873-2690
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Lipoxygenases (LOXs) are non-haem iron-containing dioxygenases that catalyse oxygenation of polyunsaturated fatty acids. This reaction is the first step in biosynthesis of oxylipins, which play important and diverse roles in stress response. In this study, we identified four LOX genes (PcLOXA, B, C, D) in chilling-sensitive runner bean (Phaseolus coccineus L.) plant and analyzed their expression patterns during long term dark-chilling (4 °C) stress and during day/night (21ºC/4 °C) temperature fluctuations. Three of the four identified LOX genes, namely PcLOXA, PcLOXB and PcLOXD, were induced by wounding stress, while only the PcLOXA was induced by dark-chilling of both detached (wounded) leaves and whole plants. We identified PcLOXA as a chloroplast-targeted LOX protein and investigated its expression during chilling stress in terms of abundance, localization inside chloroplasts and interactions with the thylakoid membranes. The analysis by immunogold electron microscopy has shown that more than 60% of detectable PcLOXA protein was associated with thylakoids, and dark-chilling of leaves resulted in increased amounts of this protein detected within grana margins of thylakoids. This effect was reversible under subsequent photo-activation of chilled leaves. PcLOXA binding to thylakoids is not mediated by the posttranslational modification but rather is based on direct interactions of the protein with membrane lipids; the binding strength increases under dark-chilling conditions.
[Mh] Termos MeSH primário: Temperatura Baixa
Luz
Lipoxigenase/metabolismo
Phaseolus/enzimologia
Proteínas de Plantas/metabolismo
Tilacoides/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Proteins); EC 1.13.11.12 (Lipoxygenase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE


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[PMID]:28471020
[Au] Autor:Pérez-Calderón J; Califano A; Santos MV; Zaritzky N
[Ad] Endereço:Centro de Investigación y Desarrollo en Criotecnología de Alimentos CIDCA (UNLP-CONICET-CIC), La Plata, Argentina, Calle 47 y 116, CP 1900, Argentina.
[Ti] Título:Kinetic Parameters for the Thermal Inactivation of Peroxidase and Lipoxygenase in Precooked Frozen Brassica Species.
[So] Source:J Food Sci;82(6):1378-1386, 2017 Jun.
[Is] ISSN:1750-3841
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Thermal inactivation of peroxidase (POD) and lipoxygenase (LOX), both enzymes present in broccoli and Brussels sprouts, is required before freezing, to obtain high-quality precooked frozen vegetables. Rate constants of a 1st-order biphasic model for the heat-labile and heat-resistant POD and LOX isoenzymes were determined at different temperatures (75, 80, and 90 °C) and the corresponding activation energies were estimated using nonlinear regressions. In the case of Brussels sprouts, the activation energies for the resistant and labile fractions were 56.3 and 62.5 kJ/mol for POD and 63.7 and 65.8 kJ/mol for LOX, respectively. For Brussels sprouts, different precooking times were tested to analyze the effect of residual enzyme activity on quality parameters and sensory attributes, after a frozen storage of 4 mo at -20 °C. A significant reactivation of enzyme activity after frozen storage was observed (especially in the case of POD) for short precooking times (<6 min) leading to low-quality parameters at the interior zone of the vegetable. A precooking time of 6 min at 90 °C allowed an adequate inactivation of LOX and POD obtaining a high-quality final frozen vegetable. A sensory analysis confirmed the global acceptability of the product. The obtained results are relevant to define the precooking stage conditions in the production of frozen cruciferous vegetables.
[Mh] Termos MeSH primário: Brassica/enzimologia
Manipulação de Alimentos/métodos
Temperatura Alta
Lipoxigenase/metabolismo
Peroxidase/metabolismo
[Mh] Termos MeSH secundário: Congelamento
Cinética
Lipoxigenase/química
Peroxidase/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.11.1.7 (Peroxidase); EC 1.13.11.12 (Lipoxygenase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1111/1750-3841.13717


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[PMID]:29053969
[Au] Autor:Wenzel SE; Tyurina YY; Zhao J; St Croix CM; Dar HH; Mao G; Tyurin VA; Anthonymuthu TS; Kapralov AA; Amoscato AA; Mikulska-Ruminska K; Shrivastava IH; Kenny EM; Yang Q; Rosenbaum JC; Sparvero LJ; Emlet DR; Wen X; Minami Y; Qu F; Watkins SC; Holman TR; VanDemark AP; Kellum JA; Bahar I; Bayir H; Kagan VE
[Ad] Endereço:Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: wenzelse@upmc.edu.
[Ti] Título:PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals.
[So] Source:Cell;171(3):628-641.e26, 2017 Oct 19.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ferroptosis is a form of programmed cell death that is pathogenic to several acute and chronic diseases and executed via oxygenation of polyunsaturated phosphatidylethanolamines (PE) by 15-lipoxygenases (15-LO) that normally use free polyunsaturated fatty acids as substrates. Mechanisms of the altered 15-LO substrate specificity are enigmatic. We sought a common ferroptosis regulator for 15LO. We discovered that PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 and 15LO2, and changes their substrate competence to generate hydroperoxy-PE. Inadequate reduction of hydroperoxy-PE due to insufficiency or dysfunction of a selenoperoxidase, GPX4, leads to ferroptosis. We demonstrated the importance of PEBP1-dependent regulatory mechanisms of ferroptotic death in airway epithelial cells in asthma, kidney epithelial cells in renal failure, and cortical and hippocampal neurons in brain trauma. As master regulators of ferroptotic cell death with profound implications for human disease, PEBP1/15LO complexes represent a new target for drug discovery.
[Mh] Termos MeSH primário: Lesão Renal Aguda/patologia
Asma/patologia
Lesões Encefálicas Traumáticas/patologia
Morte Celular
Proteína de Ligação a Fosfatidiletanolamina/metabolismo
[Mh] Termos MeSH secundário: Lesão Renal Aguda/metabolismo
Animais
Apoptose
Asma/metabolismo
Lesões Encefálicas Traumáticas/metabolismo
Morte Celular/efeitos dos fármacos
Linhagem Celular
Seres Humanos
Isoenzimas/metabolismo
Lipoxigenase/química
Lipoxigenase/metabolismo
Camundongos
Modelos Moleculares
Oxazolidinonas/farmacologia
Oxirredução
Proteína de Ligação a Fosfatidiletanolamina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Isoenzymes); 0 (Oxazolidinones); 0 (PEBP1 protein, human); 0 (Phosphatidylethanolamine Binding Protein); 0 (Raf kinase inhibitory protein, mouse); 0 (locostatin); EC 1.13.11.12 (Lipoxygenase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171115
[Lr] Data última revisão:
171115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171021
[St] Status:MEDLINE


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[PMID]:28771028
[Au] Autor:Kaur G; Silakari O
[Ad] Endereço:Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala, Punjab 147002, India.
[Ti] Título:Multiple target-centric strategy to tame inflammation.
[So] Source:Future Med Chem;9(12):1361-1376, 2017 Aug.
[Is] ISSN:1756-8927
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Single-target inhibition is an unsatisfactory therapeutic option to treat multifactorial pathologies, brought into limelight 'paradox of inflammation' beside dearth of innovation, rationalizes a shift toward 'multiple-target' design concept in anti-inflammatory research field. To improvise, two platform strategies, drugs mixture or multitarget drugs, are plausible. Dual cyclooxygenase/lipoxygenase inhibitor 'licofelone' developed after the backfire of rofecoxib due to safety concerns has fetched first light of triumph of the latter strategy. As hitting multiple targets in restraint is perhaps more viable strategy rather than single target, this review, outlines the most germane multiple target agents of synthetic and natural origin placing clear advantage in favors of multitarget strategy as real therapeutic solution for inflammation.
[Mh] Termos MeSH primário: Inibidores de Ciclo-Oxigenase/farmacologia
Inflamação/tratamento farmacológico
Lactonas/farmacologia
Inibidores de Lipoxigenase/farmacologia
Pirróis/farmacologia
Sulfonas/farmacologia
[Mh] Termos MeSH secundário: Inibidores de Ciclo-Oxigenase/síntese química
Inibidores de Ciclo-Oxigenase/química
Seres Humanos
Lactonas/síntese química
Lactonas/química
Lipoxigenase/metabolismo
Inibidores de Lipoxigenase/síntese química
Inibidores de Lipoxigenase/química
Estrutura Molecular
Prostaglandina-Endoperóxido Sintases/metabolismo
Pirróis/síntese química
Pirróis/química
Relação Estrutura-Atividade
Sulfonas/síntese química
Sulfonas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cyclooxygenase Inhibitors); 0 (Lactones); 0 (Lipoxygenase Inhibitors); 0 (Pyrroles); 0 (Sulfones); 0QTW8Z7MCR (rofecoxib); EC 1.13.11.12 (Lipoxygenase); EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases); P5T6BYS22Y (licofelone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.4155/fmc-2017-0050


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[PMID]:28759610
[Au] Autor:Dong B; Wu B; Hong W; Li X; Li Z; Xue L; Huang Y
[Ad] Endereço:South China Agricultural University, Guangzhou, Guangdong, China.
[Ti] Título:Transcriptome analysis of the tea oil camellia (Camellia oleifera) reveals candidate drought stress genes.
[So] Source:PLoS One;12(7):e0181835, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The tea-oil camellia (Camellia oleifera) is the most important oil plant in southern China, and has a strong resistance to drought and barren soil. Understanding the molecular mechanisms of drought tolerance would greatly promote its cultivation and molecular breeding. RESULTS: In total, we obtained 76,585 unigenes with an average length of 810 bp and an N50 of 1,092 bp. We mapped all the unigenes to the NCBI 'nr' (non-redundant), SwissProt, KEGG, and clusters of orthologous groups (COG) databases, where 52,531 (68.6%) unigenes were functionally annotated. According to the annotation, 46,171 (60.8%) unigenes belong to 338 KEGG pathways. We identified a series of unigenes that are related to the synthesis and regulation of abscisic acid (ABA), the activity of protective enzymes, vitamin B6 metabolism, the metabolism of osmolytes, and pathways related to the biosynthesis of secondary metabolites. After exposed to drought for 12 hours, the number of differentially-expressed genes (DEGs) between treated plants and control plants increased in the G4 cultivar, while there was no significant increase in the drought-tolerant C3 cultivar. DEGs associated with drought stress responsive pathways were identified by KEGG pathway enrichment analysis. Moreover, we found 789 DEGs related to transcription factors. Finally, according to the results of qRT-PCR, the expression levels of the 20 unigenes tested were consistent with the results of next-generation sequencing. CONCLUSIONS: In the present study, we identified a large set of cDNA unigenes from C. oleifera annotated using public databases. Further studies of DEGs involved in metabolic pathways related to drought stress and transcription will facilitate the discovery of novel genes involved in resistance to drought stress in this commercially important plant.
[Mh] Termos MeSH primário: Camellia/genética
Secas
Estresse Fisiológico/genética
Transcriptoma
[Mh] Termos MeSH secundário: Ácido Abscísico/química
China
DNA Complementar/metabolismo
Bases de Dados de Proteínas
Perfilação da Expressão Gênica
Regulação da Expressão Gênica de Plantas
Biblioteca Gênica
Genoma de Planta
Sequenciamento de Nucleotídeos em Larga Escala
Lipoxigenase/metabolismo
Malondialdeído/química
Redes e Vias Metabólicas
Análise de Componente Principal
RNA de Plantas/genética
Espécies Reativas de Oxigênio/metabolismo
Vitamina B 6/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Complementary); 0 (RNA, Plant); 0 (Reactive Oxygen Species); 4Y8F71G49Q (Malondialdehyde); 72S9A8J5GW (Abscisic Acid); 8059-24-3 (Vitamin B 6); EC 1.13.11.12 (Lipoxygenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181835



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