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[PMID]:28743542
[Au] Autor:Maia J; Almada M; Silva A; Correia-da-Silva G; Teixeira N; Sá SI; Fonseca BM
[Ad] Endereço:UCIBIO, REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
[Ti] Título:The endocannabinoid system expression in the female reproductive tract is modulated by estrogen.
[So] Source:J Steroid Biochem Mol Biol;174:40-47, 2017 11.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The endocannabinoid system (ECS) is involved in several physiological events that resulted in a growing interest in its modulation. Moreover, the uterine levels of anandamide (AEA), the major endocannabinoid, must be tightly regulated to create proper embryo implantation conditions. However, there are no evidences about the regulation of AEA in uterus by estrogen. Thus, the aim of this study is to elucidate whether estradiol benzoate (EB) and tamoxifen (TAM) administration to ovariectomized (OVX) rats can induce changes in the expression of cannabinoid receptors and AEA-metabolic enzymes in uterus by evaluating gene transcription and protein levels by qPCR, Western blot and immunohistochemistry. Moreover, the plasmatic and uterine levels of AEA and of prostaglandin E (PGE ) and prostaglandin F α (PGF ), the major cyclooxygenase-2 (COX-2) products, were determined by UPLC-MS/MS. The immunohistochemistry showed that cannabinoid receptors, as well as AEA-metabolic enzymes are mainly located in the epithelial cells of both lumen and glands and, to a lesser extent, in the muscle cells. Moreover, EB administration to OVX rats significantly increased CB1, CB2, NAPE-PLD, FAAH and COX-2 expression and transcription. These effects were absent in TAM and TAM+EB treatments showing that this response is estrogen receptor dependent. Additionally, although uterine levels of AEA remained unchanged in EB or TAM treated animals, they showed a rise with EB treatment in plasma. The latter also produced a decrease in uterine PGE levels. In summary, these data collectively indicate that the expression of ECS components, as well as, the AEA and PGE levels in rat uterus is modulated by EB. Thus, estradiol may have a direct regulatory role in the modulation of ECS in female reproductive tissues.
[Mh] Termos MeSH primário: Estradiol/análogos & derivados
Estrogênios/farmacologia
Tamoxifeno/farmacologia
Útero/efeitos dos fármacos
[Mh] Termos MeSH secundário: Amidoidrolases/genética
Amidoidrolases/metabolismo
Animais
Ácidos Araquidônicos/sangue
Ácidos Araquidônicos/metabolismo
Ciclo-Oxigenase 2/genética
Ciclo-Oxigenase 2/metabolismo
Dinoprosta/sangue
Dinoprostona/sangue
Dinoprostona/metabolismo
Endocanabinoides/sangue
Endocanabinoides/metabolismo
Estradiol/farmacologia
Feminino
Tamanho do Órgão/efeitos dos fármacos
Ovariectomia
Fosfolipase D/genética
Fosfolipase D/metabolismo
Alcamidas Poli-Insaturadas/sangue
Alcamidas Poli-Insaturadas/metabolismo
Ratos Wistar
Receptor CB1 de Canabinoide/genética
Receptor CB1 de Canabinoide/metabolismo
Receptor CB2 de Canabinoide/genética
Receptor CB2 de Canabinoide/metabolismo
Útero/metabolismo
Útero/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Arachidonic Acids); 0 (Endocannabinoids); 0 (Estrogens); 0 (Polyunsaturated Alkamides); 0 (Receptor, Cannabinoid, CB1); 0 (Receptor, Cannabinoid, CB2); 094ZI81Y45 (Tamoxifen); 1S4CJB5ZGN (estradiol 3-benzoate); 4TI98Z838E (Estradiol); B7IN85G1HY (Dinoprost); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.14.99.1 (Ptgs2 protein, rat); EC 3.1.4.4 (NAPE-PLD protein, rat); EC 3.1.4.4 (Phospholipase D); EC 3.5.- (Amidohydrolases); EC 3.5.1.- (fatty-acid amide hydrolase); K7Q1JQR04M (Dinoprostone); UR5G69TJKH (anandamide)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171208
[Lr] Data última revisão:
171208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE


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[PMID]:29053796
[Au] Autor:Nibbeling EAR; Duarri A; Verschuuren-Bemelmans CC; Fokkens MR; Karjalainen JM; Smeets CJLM; de Boer-Bergsma JJ; van der Vries G; Dooijes D; Bampi GB; van Diemen C; Brunt E; Ippel E; Kremer B; Vlak M; Adir N; Wijmenga C; van de Warrenburg BPC; Franke L; Sinke RJ; Verbeek DS
[Ad] Endereço:Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
[Ti] Título:Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia.
[So] Source:Brain;140(11):2860-2878, 2017 Nov 01.
[Is] ISSN:1460-2156
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The autosomal dominant cerebellar ataxias, referred to as spinocerebellar ataxias in genetic nomenclature, are a rare group of progressive neurodegenerative disorders characterized by loss of balance and coordination. Despite the identification of numerous disease genes, a substantial number of cases still remain without a genetic diagnosis. Here, we report five novel spinocerebellar ataxia genes, FAT2, PLD3, KIF26B, EP300, and FAT1, identified through a combination of exome sequencing in genetically undiagnosed families and targeted resequencing of exome candidates in a cohort of singletons. We validated almost all genes genetically, assessed damaging effects of the gene variants in cell models and further consolidated a role for several of these genes in the aetiology of spinocerebellar ataxia through network analysis. Our work links spinocerebellar ataxia to alterations in synaptic transmission and transcription regulation, and identifies these as the main shared mechanisms underlying the genetically diverse spinocerebellar ataxia types.
[Mh] Termos MeSH primário: Redes Reguladoras de Genes/genética
Ataxias Espinocerebelares/genética
[Mh] Termos MeSH secundário: Animais
Células COS
Caderinas/genética
Cercopithecus aethiops
Proteína p300 Associada a E1A/genética
Exoma/genética
Feminino
Células HEK293
Seres Humanos
Cinesina/genética
Masculino
Linhagem
Fosfolipase D/genética
Plasmídeos
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Análise de Sequência de DNA
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cadherins); 0 (FAT1 protein, human); 0 (FAT2 protein, human); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (EP300 protein, human); EC 3.1.4.4 (Phospholipase D); EC 3.1.4.4 (phospholipase D3, human); EC 3.6.1.- (KIF26B protein, human); EC 3.6.4.4 (Kinesin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171021
[St] Status:MEDLINE
[do] DOI:10.1093/brain/awx251


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[PMID]:29033361
[Au] Autor:Wang Z; Zhang F; He J; Wu P; Tay LWR; Cai M; Nian W; Weng Y; Qin L; Chang JT; McIntire LB; Di Paolo G; Xu J; Peng J; Du G
[Ad] Endereço:Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX 77030, USA.
[Ti] Título:Binding of PLD2-Generated Phosphatidic Acid to KIF5B Promotes MT1-MMP Surface Trafficking and Lung Metastasis of Mouse Breast Cancer Cells.
[So] Source:Dev Cell;43(2):186-197.e7, 2017 Oct 23.
[Is] ISSN:1878-1551
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Little is known about the cellular events promoting metastasis. We show that knockout of phospholipase D (PLD2), which generates the signaling lipid phosphatidic acid (PA), inhibits lung metastases in the mammary tumor virus (MMTV)-Neu transgenic mouse breast cancer model. PLD2 promotes local invasion through the regulation of the plasma membrane targeting of MT1-MMP and its associated invadopodia. A liposome pull-down screen identifies KIF5B, the heavy chain of the motor protein kinesin-1, as a new PA-binding protein. In vitro assays reveal that PA specifically and directly binds to the C terminus of KIF5B. The binding between PLD2-generated PA and KIF5B is required for the vesicular association of KIF5B, surface localization of MT1-MMP, invadopodia, and invasion in cancer cells. Taken together, these results identify a role of PLD2-generated PA in the regulation of kinesin-1 motor functions and breast cancer metastasis and suggest PLD2 as a potential therapeutic target for metastatic breast cancer.
[Mh] Termos MeSH primário: Cinesina/metabolismo
Neoplasias Pulmonares/secundário
Neoplasias Mamárias Animais/patologia
Metaloproteinase 14 da Matriz/metabolismo
Ácidos Fosfatídicos/metabolismo
Fosfolipase D/fisiologia
[Mh] Termos MeSH secundário: Animais
Membrana Celular/metabolismo
Movimento Celular/fisiologia
Feminino
Seres Humanos
Cinesina/genética
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/metabolismo
Células MCF-7
Neoplasias Mamárias Animais/genética
Neoplasias Mamárias Animais/metabolismo
Metaloproteinase 14 da Matriz/genética
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Ligação Proteica
Transporte Proteico
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phosphatidic Acids); EC 3.1.4.- (phospholipase D2); EC 3.1.4.4 (Phospholipase D); EC 3.4.24.80 (Matrix Metalloproteinase 14); EC 3.6.1.- (Kif5b protein, mouse); EC 3.6.4.4 (Kinesin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE


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[PMID]:28938452
[Au] Autor:Forner-Piquer I; Maradonna F; Gioacchini G; Santangeli S; Allarà M; Piscitelli F; Habibi HR; Di Marzo V; Carnevali O
[Ad] Endereço:Dipartimento Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, 60131 Ancona, Italy.
[Ti] Título:Dose-Specific Effects of Di-Isononyl Phthalate on the Endocannabinoid System and on Liver of Female Zebrafish.
[So] Source:Endocrinology;158(10):3462-3476, 2017 Oct 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phthalates, used as plasticizers, have become a ubiquitous contaminant and have been reported for their potential to induce toxicity in living organisms. Among them, di-isononyl phthalate (DiNP) has been recently used to replace di(2-ethylhexyl) phthalate (DEHP). Nowadays, there is evidence that DiNP is an endocrine-disrupting chemical; however, little is known about its effects on the endocannabinoid system (ECS) and lipid metabolism. Hence, the aim of our study was to investigate the effects of DiNP on the ECS in zebrafish liver and brain and on hepatic lipid storage. To do so, adult female zebrafish were exposed to three concentrations (0.42 µg/L, 4.2 µg/L, and 42 µg/L) of DiNP via water for 3 weeks. Afterwards, we investigated transcript levels for genes involved in the ECS of the brain and liver as well as liver histology and image analysis, Fourier-transform infrared spectroscopy imaging, and measurement of endocannabinoid levels. Our results demonstrate that DiNP upregulates orexigenic signals and causes hepatosteatosis together with deregulation of the peripheral ECS and lipid metabolism. A decrease in the levels of ECS components at the central level was observed after exposure to the highest DiNP concentration tested. These findings suggest that replacement of DEHP with DiNP should be considered with caution because of observed adverse DiNP effects on aquatic organisms.
[Mh] Termos MeSH primário: Encéfalo/efeitos dos fármacos
Endocanabinoides/metabolismo
Metabolismo dos Lipídeos/efeitos dos fármacos
Fígado/efeitos dos fármacos
Ácidos Ftálicos/farmacologia
Plastificantes/farmacologia
[Mh] Termos MeSH secundário: Animais
Ácidos Araquidônicos/metabolismo
Encéfalo/metabolismo
Relação Dose-Resposta a Droga
Disruptores Endócrinos/farmacologia
Fígado Gorduroso/metabolismo
Feminino
Expressão Gênica/efeitos dos fármacos
Glicerídeos/metabolismo
Lipase Lipoproteica/efeitos dos fármacos
Lipase Lipoproteica/genética
Lipase Lipoproteica/metabolismo
Fosfolipase D/efeitos dos fármacos
Fosfolipase D/genética
Fosfolipase D/metabolismo
Alcamidas Poli-Insaturadas/metabolismo
Receptor CB1 de Canabinoide/efeitos dos fármacos
Receptor CB1 de Canabinoide/genética
Receptor CB1 de Canabinoide/metabolismo
Receptor CB2 de Canabinoide/efeitos dos fármacos
Receptor CB2 de Canabinoide/genética
Receptor CB2 de Canabinoide/metabolismo
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arachidonic Acids); 0 (Endocannabinoids); 0 (Endocrine Disruptors); 0 (Glycerides); 0 (Phthalic Acids); 0 (Plasticizers); 0 (Polyunsaturated Alkamides); 0 (Receptor, Cannabinoid, CB1); 0 (Receptor, Cannabinoid, CB2); 4010KIX4CK (diisononyl phthalate); 8D239QDW64 (glyceryl 2-arachidonate); EC 3.1.1.34 (Lipoprotein Lipase); EC 3.1.4.4 (N-acylphosphatidylethanolamine phospholipase D, mouse); EC 3.1.4.4 (Phospholipase D); UR5G69TJKH (anandamide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00458


  5 / 3846 MEDLINE  
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[PMID]:28926616
[Au] Autor:Liu M; Clarke CJ; Salama MF; Choi YJ; Obeid LM; Hannun YA
[Ad] Endereço:Department of Medicine, Stony Brook University, Stony Brook, NY, United States of America.
[Ti] Título:Co-ordinated activation of classical and novel PKC isoforms is required for PMA-induced mTORC1 activation.
[So] Source:PLoS One;12(9):e0184818, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Protein kinase C (PKC) has been shown to activate the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, a central hub in the regulation of cell metabolism, growth and proliferation. However, the mechanisms by which PKCs activate mTORC1 are still ambiguous. Our previous study revealed that activation of classical PKCs (cPKC) results in the perinuclear accumulation of cPKC and phospholipase D2 (PLD2) in recycling endosomes in a PLD2-dependent manner. Here, we report that mTORC1 activation by phorbol 12,13-myristate acetate (PMA) requires both classic, cPKC, and novel PKC (nPKC) isoforms, specifically PKCη, acting through distinct pathways. The translocation of mTOR to perinuclear lysosomes was detected after treatment of PKC activators, which was not colocalized with PKCα- or RAB11-positive endosomes and was not inhibited by PLD inhibitors. We found that PKCη inhibition by siRNA or bisindolylmaleimide I effectively decreased mTOR accumulation in lysosomes and its activity. Also, we identified that PKCη plays a role upstream of the v-ATPase/Ragulator/Rag pathway in response to PMA. These data provides a spatial aspect to the regulation of mTORC1 by sustained activation of PKC, requiring co-ordinated activation of two distinct elements, the perinuclear accumulation of cPKC- and PLD-containing endosomes and the nPKC-dependent translation of of mTOR in the perinuclear lysosomes. The close proximity of these two distinct compartments shown in this study suggests the possibility that transcompartment signaling may be a factor in the regulation of mTORC1 activity and also underscores the importance of PKCη as a potential therapeutic target of mTORC-related disorders.
[Mh] Termos MeSH primário: Complexos Multiproteicos/metabolismo
Proteína Quinase C/metabolismo
Serina-Treonina Quinases TOR/metabolismo
Acetato de Tetradecanoilforbol/farmacologia
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/metabolismo
Carbazóis/farmacologia
Endocitose/efeitos dos fármacos
Endossomos/metabolismo
Ativação Enzimática/efeitos dos fármacos
Células HEK293
Células HeLa
Seres Humanos
Lisossomos/metabolismo
Alvo Mecanístico do Complexo 1 de Rapamicina
Fosfolipase D/metabolismo
Fosforilação/efeitos dos fármacos
Isoformas de Proteínas/antagonistas & inibidores
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Proteína Quinase C/antagonistas & inibidores
Proteína Quinase C/genética
Interferência de RNA
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbazoles); 0 (Multiprotein Complexes); 0 (Protein Isoforms); 136194-77-9 (Go 6976); EC 2.7.1.- (protein kinase C eta); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1); EC 2.7.11.13 (Protein Kinase C); EC 3.1.4.- (phospholipase D2); EC 3.1.4.4 (Phospholipase D); EC 3.6.1.- (Adenosine Triphosphatases); NI40JAQ945 (Tetradecanoylphorbol Acetate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184818


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[PMID]:28892824
[Au] Autor:Lippestad M; Hodges RR; Utheim TP; Serhan CN; Dartt DA
[Ad] Endereço:Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
[Ti] Título:Resolvin D1 Increases Mucin Secretion in Cultured Rat Conjunctival Goblet Cells via Multiple Signaling Pathways.
[So] Source:Invest Ophthalmol Vis Sci;58(11):4530-4544, 2017 Sep 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Goblet cells in the conjunctiva secrete mucin into the tear film protecting the ocular surface. The proresolution mediator resolvin D1 (RvD1) regulates mucin secretion to maintain homeostasis during physiological conditions and in addition, actively terminates inflammation. We determined the signaling mechanisms used by RvD1 in cultured rat conjunctival goblet cells to increase intracellular [Ca2+] ([Ca2+]i) and induce glycoconjugate secretion. Methods: Increase in [Ca2+]i were measured using fura 2/AM and glycoconjugate secretion determined using an enzyme-linked lectin assay with the lectin Ulex Europaeus Agglutinin 1. Signaling pathways activated by RvD1 were studied after goblet cells were pretreated with signaling pathway inhibitors before stimulation with RvD1. The results were compared with results when goblet cells were stimulated with RvD1 alone and percent inhibition calculated. Results: The increase in [Ca2+]i stimulated by RvD1 was blocked by inhibitors to phospholipases (PL-) -D, -C, -A2, protein kinase C (PKC), extracellular signal-regulated kinases (ERK)1/2 and Ca2+/calmodulin-dependent kinase (Ca2+/CamK). Glycoconjugate secretion was significantly inhibited by PLD, -C, -A2, ERK1/2 and Ca2+/CamK, but not PKC. Conclusions: We conclude that RvD1 increases glycoconjugate secretion from goblet cells via multiple signaling pathways including PLC, PLD, and PLA2, as well as their signaling components ERK1/2 and Ca2+/CamK to preserve the mucous layer and maintain homeostasis by protecting the eye from desiccating stress, allergens, and pathogens.
[Mh] Termos MeSH primário: Túnica Conjuntiva/efeitos dos fármacos
Ácidos Docosa-Hexaenoicos/farmacologia
Células Caliciformes/efeitos dos fármacos
Mucinas/secreção
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Animais
Cálcio/metabolismo
Células Cultivadas
Túnica Conjuntiva/metabolismo
Ensaio de Imunoadsorção Enzimática
Fura-2/análogos & derivados
Fura-2/metabolismo
Células Caliciformes/metabolismo
Receptores de Inositol 1,4,5-Trifosfato/metabolismo
Sistema de Sinalização das MAP Quinases/fisiologia
Masculino
Fosfolipase D/metabolismo
Fosfolipases A2/metabolismo
Ratos
Ratos Sprague-Dawley
Receptores de Lipoxinas/metabolismo
Fosfolipases Tipo C/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Inositol 1,4,5-Trisphosphate Receptors); 0 (Mucins); 0 (Receptors, Lipoxin); 0 (lipoxin A(4) receptor, rat); 0 (resolvin D1); 105344-37-4 (fura-2-am); 25167-62-8 (Docosahexaenoic Acids); EC 3.1.1.4 (Phospholipases A2); EC 3.1.4.- (Type C Phospholipases); EC 3.1.4.4 (Phospholipase D); SY7Q814VUP (Calcium); TSN3DL106G (Fura-2)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-21914


  7 / 3846 MEDLINE  
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[PMID]:28822840
[Au] Autor:Chakraborti S; Sarkar J; Chowdhury A; Chakraborti T
[Ad] Endereço:Department of Biochemistry and Biophysics, University of Kalyani, Kalyani 741235, West Bengal, India. Electronic address: sajal_chakraborti@yahoo.com.
[Ti] Título:Role of ADP ribosylation factor6- Cytohesin1-PhospholipaseD signaling axis in U46619 induced activation of NADPH oxidase in pulmonary artery smooth muscle cell membrane.
[So] Source:Arch Biochem Biophys;633:1-14, 2017 Nov 01.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Treatment of human pulmonary artery smooth muscle cells (HPASMCs) with the thromboxane A2 receptor antagonist, SQ29548 inhibited U46619 stimulation of phospholipase D (PLD) and NADPH oxidase activities in the cell membrane. Pretreatment with apocynin inhibited U46619 induced increase in NADPH oxidase activity. The cell membrane contains predominantly PLD2 along with PLD1 isoforms of PLD. Pretreatment with pharmacological and genetic inhibitors of PLD2, but not PLD1, attenuated U46619 stimulation of NADPH oxidase activity. U46619 stimulation of PLD and NADPH oxidase activities were insensitive to BFA and Clostridium botulinum C3 toxin; however, pretreatment with secinH3 inhibited U46619 induced increase in PLD and NADPH oxidase activities suggesting a major role of cytohesin in U46619-induced increase in PLD and NADPH oxidase activities. Arf-1, Arf-6, cytohesin-1 and cytohesin-2 were observed in the cytosolic fraction, but only Arf-6 and cytohesin-1 were translocated to the cell membrane upon treatment with U46619. Coimmunoprecipitation study showed association of Arf-6 with cytohesin-1 in the cell membrane fraction. In vitro binding of GTPγS with Arf-6 required the presence of cytohesin-1 and that occurs in BFA insensitive manner. Overall, BFA insensitive Arf6-cytohesin1 signaling axis plays a pivotal role in U46619-mediated activation of PLD leading to stimulation of NADPH oxidase activity in HPASMCs.
[Mh] Termos MeSH primário: Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia
Fatores de Ribosilação do ADP/genética
Fatores de Troca do Nucleotídeo Guanina/genética
NADPH Oxidases/genética
Fosfolipase D/genética
Vasoconstritores/farmacologia
[Mh] Termos MeSH secundário: ADP Ribose Transferases/farmacologia
Fatores de Ribosilação do ADP/metabolismo
Acetofenonas/farmacologia
Antioxidantes/farmacologia
Toxinas Botulínicas/farmacologia
Brefeldina A/farmacologia
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Proteínas Ativadoras de GTPase/antagonistas & inibidores
Proteínas Ativadoras de GTPase/genética
Proteínas Ativadoras de GTPase/metabolismo
Regulação da Expressão Gênica
Fatores de Troca do Nucleotídeo Guanina/antagonistas & inibidores
Fatores de Troca do Nucleotídeo Guanina/metabolismo
Guanosina 5'-O-(3-Tiotrifosfato)/farmacologia
Seres Humanos
Hidrazinas/farmacologia
Miócitos de Músculo Liso/citologia
Miócitos de Músculo Liso/efeitos dos fármacos
Miócitos de Músculo Liso/metabolismo
NADPH Oxidases/metabolismo
Fosfolipase D/antagonistas & inibidores
Fosfolipase D/metabolismo
Cultura Primária de Células
Inibidores da Síntese de Proteínas/farmacologia
Artéria Pulmonar/citologia
Artéria Pulmonar/efeitos dos fármacos
Artéria Pulmonar/metabolismo
Receptores de Tromboxano A2 e Prostaglandina H2/antagonistas & inibidores
Receptores de Tromboxano A2 e Prostaglandina H2/genética
Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo
Transdução de Sinais
Triazóis/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetophenones); 0 (Antioxidants); 0 (GTPase-Activating Proteins); 0 (Guanine Nucleotide Exchange Factors); 0 (Hydrazines); 0 (Protein Synthesis Inhibitors); 0 (Receptors, Thromboxane A2, Prostaglandin H2); 0 (SecinH3); 0 (Triazoles); 0 (Vasoconstrictor Agents); 0 (cytohesin-1); 0 (cytohesin-2); 20350-15-6 (Brefeldin A); 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)); 76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid); 98299-61-7 (SQ 29548); B6J7B9UDTR (acetovanillone); EC 1.6.3.- (NADPH Oxidases); EC 2.4.2.- (ADP Ribose Transferases); EC 2.4.2.- (exoenzyme C3, Clostridium botulinum); EC 3.1.4.- (phospholipase D2); EC 3.1.4.4 (Phospholipase D); EC 3.1.4.4 (phospholipase D1); EC 3.4.24.69 (Botulinum Toxins); EC 3.6.5.2 (ADP-Ribosylation Factors); EC 3.6.5.2 (ADP-ribosylation factor 6)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170821
[St] Status:MEDLINE


  8 / 3846 MEDLINE  
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[PMID]:28749988
[Au] Autor:Inoue K; Ichiyanagi K; Fukuda K; Glinka M; Sasaki H
[Ad] Endereço:Division of Epigenomics and Development, Medical Institute of Bioregulation and Epigenome Network Research Center, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan.
[Ti] Título:Switching of dominant retrotransposon silencing strategies from posttranscriptional to transcriptional mechanisms during male germ-cell development in mice.
[So] Source:PLoS Genet;13(7):e1006926, 2017 Jul.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mammalian genomes harbor millions of retrotransposon copies, some of which are transpositionally active. In mouse prospermatogonia, PIWI-interacting small RNAs (piRNAs) combat retrotransposon activity to maintain the genomic integrity. The piRNA system destroys retrotransposon-derived RNAs and guides de novo DNA methylation at some retrotransposon promoters. However, it remains unclear whether DNA methylation contributes to retrotransposon silencing in prospermatogonia. We have performed comprehensive studies of DNA methylation and polyA(+) RNAs (transcriptome) in developing male germ cells from Pld6/Mitopld and Dnmt3l knockout mice, which are defective in piRNA biogenesis and de novo DNA methylation, respectively. The Dnmt3l mutation greatly reduced DNA methylation levels at most retrotransposons, but its impact on their RNA abundance was limited in prospermatogonia. In Pld6 mutant germ cells, although only a few retrotransposons exhibited reduced DNA methylation, many showed increased expression at the RNA level. More detailed analysis of RNA sequencing, nascent RNA quantification, profiling of cleaved RNA ends, and the results obtained from double knockout mice suggest that PLD6 works mainly at the posttranscriptional level. The increase in retrotransposon expression was larger in Pld6 mutants than it was in Dnmt3l mutants, suggesting that RNA degradation by the piRNA system plays a more important role than does DNA methylation in prospermatogonia. However, DNA methylation had a long-term effect: hypomethylation caused by the Pld6 or Dnmt3l mutation resulted in increased retrotransposon expression in meiotic spermatocytes. Thus, posttranscriptional silencing plays an important role in the early stage of germ cell development, then transcriptional silencing becomes important in later stages. In addition, intergenic and intronic retrotransposon sequences, in particular those containing the antisense L1 promoters, drove ectopic expression of nearby genes in both mutant spermatocytes, suggesting that retrotransposon silencing is important for the maintenance of not only genomic integrity but also transcriptomic integrity.
[Mh] Termos MeSH primário: DNA (Citosina-5-)-Metiltransferases/genética
Metilação de DNA/genética
Células Germinativas/crescimento & desenvolvimento
Proteínas Mitocondriais/genética
Fosfolipase D/genética
Transcrição Genética
[Mh] Termos MeSH secundário: Animais
Regulação da Expressão Gênica no Desenvolvimento
Masculino
Camundongos
Camundongos Knockout
Interferência de RNA
Estabilidade de RNA/genética
RNA Interferente Pequeno/genética
Retroelementos/genética
Espermatócitos/crescimento & desenvolvimento
Testículo/crescimento & desenvolvimento
Testículo/metabolismo
Transcriptoma/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mitochondrial Proteins); 0 (RNA, Small Interfering); 0 (Retroelements); EC 2.1.1.- (Dnmt3l protein, mouse); EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases); EC 3.1.4.4 (Phospholipase D); EC 3.1.4.4 (mitoPLD protein, mouse)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006926


  9 / 3846 MEDLINE  
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[PMID]:28648601
[Au] Autor:Nakagawa H; Hazama K; Ishida K; Komori M; Nishimura K; Matsuo S
[Ad] Endereço:Laboratory of Toxicology, Graduate School of Veterinary Sciences, Osaka Prefecture University, Japan. Electronic address: nakagawa@vet.osakafu-u.ac.jp.
[Ti] Título:Inhibition of PLD1 activity causes ER stress via regulation of COPII vesicle formation.
[So] Source:Biochem Biophys Res Commun;490(3):895-900, 2017 Aug 26.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phospholipase D (PLD) plays a crucial role in the regulation of some cellular processes, including autophagy and apoptosis. Accumulation of protein in the endoplasmic reticulum (ER) lumen causes ER stress. Although ER stress is a principal cause of apoptosis and autophagy, the relationship between PLD activity and ER stress remains unclear. Protein transport from the ER to the Golgi apparatus is conducted by coat complex II (COPII) transport vesicles. Here, we demonstrated that inhibition of PLD1 activity or PLD1 knockdown suppressed COPII vesicle transport in normal rat kidney (NRK) cells. COPII vesicle coat proteins are composed of Sar1 as well as Sec23/24 and Sec13/31 complexes. For COPII vesicle formation on the ER membrane, Sar1, Sec23/24, and Sec13/31 are sequentially recruited from the cytosol to the ER membrane. Using a cell-free COPII coat protein recruitment assay, we demonstrated that inhibition of PLD1 activity suppressed Sec13/31 recruitment from the cytosol to the ER membrane in COPII vesicle formation. PLD1 knockdown in NRK cells was associated with increased expression of the ER stress marker GRP78 and apoptosis. Taken together, these results suggest that PLD1 activity regulates COPII vesicle transport from the ER to the Golgi apparatus by regulating Sec13/31 recruitment from the cytosol to the ER membrane during COPII vesicle formation.
[Mh] Termos MeSH primário: Vesículas Revestidas pelo Complexo de Proteína do Envoltório/metabolismo
Estresse do Retículo Endoplasmático
Fosfolipase D/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Citosol/metabolismo
Retículo Endoplasmático/genética
Retículo Endoplasmático/metabolismo
Técnicas de Silenciamento de Genes
Complexo de Golgi/genética
Complexo de Golgi/metabolismo
Masculino
Fosfolipase D/genética
Transporte Proteico
Interferência de RNA
RNA Interferente Pequeno/genética
Ratos Sprague-Dawley
Proteínas de Transporte Vesicular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Small Interfering); 0 (Sec13 protein, rat); 0 (Vesicular Transport Proteins); EC 3.1.4.4 (Phospholipase D); EC 3.1.4.4 (phospholipase D1)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE


  10 / 3846 MEDLINE  
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[PMID]:28335389
[Au] Autor:Torabi E; Behdani M; Chafi MH; Moazzami R; Sabatier JM; Khalaj V; Shahbazzadeh D; Bagheri KP
[Ad] Endereço:Venom and Biotherapeutics Molecules Lab., Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran 13169-43551, Iran. e.torabi88@gmail.com.
[Ti] Título:Characteristics and Lethality of a Novel Recombinant  Dermonecrotic Venom Phospholipase D from  Hemiscorpius lepturus.
[So] Source:Toxins (Basel);9(3), 2017 Mar 13.
[Is] ISSN:2072-6651
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Hemoscorpius lepturus is the most medically important scorpion in Iran. The clinical signs of H. lepturus envenomation are remarkably similar to those reported for brown spiders, including dermonecrosis, hematuria, renal failure and even death. The lethality and toxicity of brown spiders' venom have been attributed to its phospholipase D activity. This study aims to identify a phospholipase D with possible lethality and dermonecrotic activity in H. lepturus venom. In this study, a cDNA library of the venom glands was generated by Illumina RNA sequencing. Phospholipase D (PLD) from H. lepturus was characterized according to its significant similarity with PLDs from brown spiders. The main chain designated as Hl-RecPLD1 (the first recombinant isoform of H. lepturus PLD) was cloned, expressed and purified. Sphingomyelinase, dermonecrotic and lethal activities were examined. Hl-PLD1 showed remarkable sequence similarity and structural homology with PLDs of brown spiders. The conformation of Hl-PLD1 was predicted as a "TIM beta/alpha-barrel". The lethal dose 50 (LD50) and dermonecrotic activities of Hl-RecPLD1 were determined as 3.1 µg/mouse and 0.7 cm2 at 1 µg respectively. It is the first report indicating that a similar molecular evolutionary mechanism has occurred in both American brown spiders and this Iranian scorpion. In conclusion, Hl-RecPLD1 is a highly active phospholipase D, which would be considered as the lethal dermonecrotic toxin in H. lepturus venom.
[Mh] Termos MeSH primário: Proteínas de Artrópodes
Fosfolipase D
Venenos de Escorpião
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Anticorpos/imunologia
Proteínas de Artrópodes/química
Proteínas de Artrópodes/genética
Proteínas de Artrópodes/metabolismo
Proteínas de Artrópodes/toxicidade
Sequência de Bases
Feminino
Hemólise/efeitos dos fármacos
Cavalos
Seres Humanos
Soros Imunes/imunologia
Dose Letal Mediana
Masculino
Camundongos Endogâmicos BALB C
Fosfolipase D/química
Fosfolipase D/genética
Fosfolipase D/metabolismo
Fosfolipase D/toxicidade
Coelhos
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Proteínas Recombinantes/toxicidade
Venenos de Escorpião/imunologia
Escorpiões
Pele/efeitos dos fármacos
Esfingomielina Fosfodiesterase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (Arthropod Proteins); 0 (Immune Sera); 0 (Recombinant Proteins); 0 (Scorpion Venoms); EC 3.1.4.12 (Sphingomyelin Phosphodiesterase); EC 3.1.4.4 (Phospholipase D)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE



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