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[PMID]:29277915
[Au] Autor:Zhang X; Ping HY; Li JH; Duan SX; Jiang XW
[Ad] Endereço:Department of Pediatric Surgery, The Affiliated Maternal and Child Health Hospital of Shenzhen University Medical College, Shenzhen, China.
[Ti] Título:Diethylstilbestrol regulates mouse gubernaculum testis cell proliferation via PLC-Ca -CREB pathway.
[So] Source:Cell Biochem Funct;36(1):13-17, 2018 Jan.
[Is] ISSN:1099-0844
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Recent evidence suggested a positive correlation between environmental estrogens (EEs) and high incidence of abnormalities in male urogenital system, but the mechanism remains unclear. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the morphology and proliferation of gubernaculum testis cells, but the underlying mechanism is unclear. In this study, mouse gubernaculum testis cells were pretreated with phospholipase C (PLC) inhibitor U-73122 and then treated with DES. The results demonstrated that U-73122 impaired DES-evoked intracellular Ca2+ mobilization in gubernaculum testis cells and inhibited DES-induced proliferation of gubernaculum testis cells. Mechanistically, we found that U-73122 inhibited DES-induced activation of cAMP-response element binding protein (CREB) in gubernaculum testis cells. In conclusion, these data suggest that the effects of DES on mouse gubernaculum testis cells are mediated by PLC-Ca -CREB pathway. SIGNIFICANCE OF THE STUDY: Environmental estrogens remain a serious threat to male reproductive health, and it is important to understand the mechanism by which EEs affect the male productive system. Here we explore potential mechanisms how the proliferation and contractility of gubernaculum testis cells are regulated by diethylstilbestrol. Our findings provide the first evidence that PLC-Ca -CREB signalling pathway mediates the nongenomic effects of diethylstilbestrol on gubernaculum testis cells. These findings provide new insight into the role of diethylstilbestrol in the aetiology of male reproductive dysfunction and will help develop better approaches for the prevention and therapy of male reproductive malformation.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
Dietilestilbestrol/farmacologia
Gubernáculo/efeitos dos fármacos
Testículo/efeitos dos fármacos
Fosfolipases Tipo C/metabolismo
[Mh] Termos MeSH secundário: Animais
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Estrenos/farmacologia
Gubernáculo/citologia
Gubernáculo/metabolismo
Masculino
Camundongos
Pirrolidinonas/farmacologia
Testículo/citologia
Testículo/metabolismo
Fosfolipases Tipo C/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclic AMP Response Element-Binding Protein); 0 (Estrenes); 0 (Pyrrolidinones); 112648-68-7 (1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione); 731DCA35BT (Diethylstilbestrol); EC 3.1.4.- (Type C Phospholipases); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE
[do] DOI:10.1002/cbf.3312


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[PMID]:29366789
[Au] Autor:Kim MS; Shin DM; Kim MS
[Ad] Endereço:Center for Metabolic Function Regulation, Wonkwang University, School of Medicine, No. 460 Iksan-Daero, Iksan, Jeonbuk 54538, Republic of Korea.
[Ti] Título:Acidification induces OGR1/Ca /calpain signaling in gingival fibroblasts.
[So] Source:Biochem Biophys Res Commun;496(2):693-699, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gingivitis, the mildest form of periodontitis, is generally considered a consequence of prolonged exposure of the gingiva to periodontal pathogens. On the other hand, several epidemiologic reports have suggested that other etiologic factors such as oral acidification may also increase the susceptibility of the periodontium to destruction. However, the pathologic mechanism underlying the effects of oral acidification on the gingiva is still largely unknown. In this study, we analyzed molecular pathways mediating the influence of the acidic environment on human gingival fibroblasts (HGFs). Acidic extracellular pH caused biphasic increase of intracellular Ca level ([Ca ] ) through activation of ovarian cancer G protein-coupled receptor 1, phospholipase C, and Ca release from the endoplasmic reticulum, but not through voltage-gated Ca channels or extracellular Ca influx via transient receptor potential cation channel subfamily V member 1. The acidic environment was also transiently cytotoxic for HGFs; however, the activation of pro-apoptotic proteins poly (ADP-ribose) polymerase-1 and BAX was not observed. Furthermore, we found that intracellular matrix metalloproteinase 1 was consistently upregulated in HGFs grown in regular medium, but significantly reduced in the acidic medium, which depended on [Ca ] increase, lysosomal pH homeostasis, and Ca -dependent protease calpain. Considering that HGFs, essential for oral wound healing, in the in vitro culture system are placed in wound repair-like conditions, our findings provide important insights into molecular mechanisms underlying HGF functional impairment and chronic damage to the gingiva caused by the acidic intraoral environment.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Calpaína/metabolismo
Fibroblastos/citologia
Gengiva/citologia
Receptores Acoplados a Proteínas-G/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Linhagem Celular
Fibroblastos/metabolismo
Gengiva/metabolismo
Seres Humanos
Concentração de Íons de Hidrogênio
Lisossomos/metabolismo
Metaloproteinase 1 da Matriz/metabolismo
Fosfolipases Tipo C/metabolismo
Cicatrização
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (GPR68 protein, human); 0 (Receptors, G-Protein-Coupled); EC 3.1.4.- (Type C Phospholipases); EC 3.4.22.- (Calpain); EC 3.4.24.7 (Matrix Metalloproteinase 1); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE


  3 / 11638 MEDLINE  
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[PMID]:28463110
[Au] Autor:Gong B; Shen W; Xiao W; Meng Y; Meng A; Jia S
[Ad] Endereço:State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
[Ti] Título:The Sec14-like phosphatidylinositol transfer proteins Sec14l3/SEC14L2 act as GTPase proteins to mediate Wnt/Ca signaling.
[So] Source:Elife;6, 2017 05 02.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The non-canonical Wnt/Ca signaling pathway plays important roles in embryonic development, tissue formation and diseases. However, it is unclear how the Wnt ligand-stimulated, G protein-coupled receptor Frizzled activates phospholipases for calcium release. Here, we report that the zebrafish/human phosphatidylinositol transfer protein Sec14l3/SEC14L2 act as GTPase proteins to transduce Wnt signals from Frizzled to phospholipase C (PLC). Depletion of attenuates Wnt/Ca responsive activity and causes convergent and extension (CE) defects in zebrafish embryos. Biochemical analyses in mammalian cells indicate that Sec14l3-GDP forms complex with Frizzled and Dishevelled; Wnt ligand binding of Frizzled induces translocation of Sec14l3 to the plasma membrane; and then Sec14l3-GTP binds to and activates phospholipase Cδ4a (Plcδ4a); subsequently, Plcδ4a initiates phosphatidylinositol-4,5-bisphosphate (PIP ) signaling, ultimately stimulating calcium release. Furthermore, Plcδ4a can act as a GTPase-activating protein to accelerate the hydrolysis of Sec14l3-bound GTP to GDP. Our data provide a new insight into GTPase protein-coupled Wnt/Ca signaling transduction.
[Mh] Termos MeSH primário: Sinalização do Cálcio
Proteínas de Transporte/metabolismo
GTP Fosfo-Hidrolases/metabolismo
Lipoproteínas/metabolismo
Proteínas de Transferência de Fosfolipídeos/metabolismo
Transativadores/metabolismo
Via de Sinalização Wnt
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Receptores Frizzled/metabolismo
Seres Humanos
Fosfolipases Tipo C/metabolismo
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Frizzled Receptors); 0 (Lipoproteins); 0 (Phospholipid Transfer Proteins); 0 (SEC14L2 protein, human); 0 (SEC14L3 protein, human); 0 (Trans-Activators); EC 3.1.4.- (Type C Phospholipases); EC 3.6.1.- (GTP Phosphohydrolases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180211
[Lr] Data última revisão:
180211
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  4 / 11638 MEDLINE  
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[PMID]:27777035
[Au] Autor:Zhu Q; Sun L; Lian J; Gao X; Zhao L; Ding M; Li J; Liang Y
[Ad] Endereço:College of Plant Protection, Shandong Agricultural University, Taian 271018, China.
[Ti] Título:The phospholipase C (FgPLC1) is involved in regulation of development, pathogenicity, and stress responses in Fusarium graminearum.
[So] Source:Fungal Genet Biol;97:1-9, 2016 12.
[Is] ISSN:1096-0937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phospholipase C (PLC) is an important phospholipid hydrolase that plays critical roles in various biological processes in eukaryotic cells. To elucidate the functions of PLC in morphogenesis and pathogenesis in Fusarium graminearum, deletion mutants were constructed of all six FgPLC genes identified in this study. Deletion of FgPLC1, but not the other five FgPLC genes, affected hyphal growth and conidiation. The FgPLC1 deletion mutant (Δplc1) also was defective in conidium germination and germ tube growth. It was sterile in selfing crosses and had increased sensitivities to hyperosmotic and cell wall stresses. The Δplc1 mutant showed reduced DON production and virulence during infection in flowering wheat heads. Deletion of FgPLC1 decreased the phosphorylation levels of both Gpmk1 and Mgv1 MAP kinases. qRT-PCR analysis showed that several genes related to defective phenotypes were down-regulated in the Δplc1 mutant. Taken together, these results indicated that FgPLC1 is important for hyphal growth, plant infection, and sexual or asexual reproduction, and it may be functionally related to MAP kinases in F. graminearum.
[Mh] Termos MeSH primário: Fusarium/genética
Doenças das Plantas/genética
Esporos Fúngicos/genética
Fosfolipases Tipo C/genética
[Mh] Termos MeSH secundário: Parede Celular/genética
Parede Celular/microbiologia
Fusarium/crescimento & desenvolvimento
Fusarium/patogenicidade
Regulação Fúngica da Expressão Gênica
Proteínas Quinases Ativadas por Mitógeno/genética
Fosforilação
Doenças das Plantas/microbiologia
Reprodução Assexuada/genética
Deleção de Sequência
Esporos Fúngicos/crescimento & desenvolvimento
Esporos Fúngicos/patogenicidade
Triticum/genética
Triticum/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 2.7.11.24 (Mitogen-Activated Protein Kinases); EC 3.1.4.- (Type C Phospholipases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171214
[Lr] Data última revisão:
171214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE


  5 / 11638 MEDLINE  
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[PMID]:28988115
[Au] Autor:Park YJ; Kim HS; Lee HY; Hwang JS; Bae YS
[Ad] Endereço:Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea.
[Ti] Título:A novel antimicrobial peptide isolated from centipede Scolopendra subspinipes mutilans stimulates neutrophil activity through formyl peptide receptor 2.
[So] Source:Biochem Biophys Res Commun;494(1-2):352-357, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this study, we identified scolopendrasin X, a novel antimicrobial peptide (AMP), from centipede Scolopendra subspinipes mutilans. Scolopendrasin X strongly stimulated mouse neutrophils, resulting in intracellular calcium increase, chemotactic migration through pertussis toxin-sensitive G-protein and phospholipase C pathway, and increased superoxide anion production in neutrophils. Target receptor for scolopendrasin X, formyl peptide receptor (FPR)2 mediated scolopendrasin X-induced neutrophil activation. Moreover, scolopendrasin X significantly blocked inflammatory cytokine production induced by lipopolysaccharide in mouse neutrophils. Taken together, our results suggest that the novel AMP scolopendrasin X can be used as a material to regulate neutrophil activity through FPR2.
[Mh] Termos MeSH primário: Peptídeos Catiônicos Antimicrobianos/farmacologia
Lipopolissacarídeos/antagonistas & inibidores
Ativação de Neutrófilo/efeitos dos fármacos
Neutrófilos/efeitos dos fármacos
Receptores de Formil Peptídeo/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Peptídeos Catiônicos Antimicrobianos/isolamento & purificação
Artrópodes/química
Cálcio/metabolismo
Quimiotaxia/efeitos dos fármacos
Proteínas de Ligação ao GTP/genética
Proteínas de Ligação ao GTP/imunologia
Lipopolissacarídeos/farmacologia
Camundongos
Camundongos Endogâmicos C57BL
Neutrófilos/citologia
Neutrófilos/imunologia
Cultura Primária de Células
Receptores de Formil Peptídeo/agonistas
Receptores de Formil Peptídeo/imunologia
Superóxidos/metabolismo
Fosfolipases Tipo C/genética
Fosfolipases Tipo C/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimicrobial Cationic Peptides); 0 (Lipopolysaccharides); 0 (Receptors, Formyl Peptide); 0 (formyl peptide receptor 2, mouse); 0 (scolopendrasin X, Scolopendra subspinipes mutilans); 11062-77-4 (Superoxides); EC 3.1.4.- (Type C Phospholipases); EC 3.6.1.- (GTP-Binding Proteins); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171009
[St] Status:MEDLINE


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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 / 11638 MEDLINE  
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[PMID]:28700916
[Au] Autor:Mohan K; Nosbisch JL; Elston TC; Bear JE; Haugh JM
[Ad] Endereço:Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina.
[Ti] Título:A Reaction-Diffusion Model Explains Amplification of the PLC/PKC Pathway in Fibroblast Chemotaxis.
[So] Source:Biophys J;113(1):185-194, 2017 Jul 11.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During the proliferative phase of cutaneous wound healing, dermal fibroblasts are recruited into the clotted wound by a concentration gradient of platelet-derived growth factor (PDGF), together with other spatial cues. Despite the importance of this chemotactic process, the mechanisms controlling the directed migration of slow-moving mesenchymal cells such as fibroblasts are not well understood. Here, we develop and analyze a reaction-diffusion model of phospholipase C/protein kinase C (PKC) signaling, which was recently identified as a requisite PDGF-gradient-sensing pathway, with the goal of identifying mechanisms that can amplify its sensitivity in the shallow external gradients typical of chemotaxis experiments. We show that phosphorylation of myristoylated alanine-rich C kinase substrate by membrane-localized PKC constitutes a positive feedback that is sufficient for local pathway amplification. The release of phosphorylated myristoylated alanine-rich C kinase substrate and its subsequent diffusion and dephosphorylation in the cytosol also serves to suppress the pathway in down-gradient regions of the cell. By itself, this mechanism only weakly amplifies signaling in a shallow PDGF gradient, but it synergizes with other feedback mechanisms to enhance amplification. This model offers a framework for a mechanistic understanding of phospholipase C/PKC signaling in chemotactic gradient sensing and can guide the design of experiments to assess the roles of putative feedback loops.
[Mh] Termos MeSH primário: Quimiotaxia/fisiologia
Fibroblastos/enzimologia
Modelos Biológicos
Proteína Quinase C/metabolismo
Fosfolipases Tipo C/metabolismo
[Mh] Termos MeSH secundário: Animais
Membrana Celular/metabolismo
Difusão
Retroalimentação Fisiológica/fisiologia
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Proteínas de Membrana/metabolismo
Substrato Quinase C Rico em Alanina Miristoilada
Fosforilação
Fator de Crescimento Derivado de Plaquetas/metabolismo
Transdução de Sinais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intracellular Signaling Peptides and Proteins); 0 (Membrane Proteins); 0 (Platelet-Derived Growth Factor); 125267-21-2 (Myristoylated Alanine-Rich C Kinase Substrate); EC 2.7.11.13 (Protein Kinase C); EC 3.1.4.- (Type C Phospholipases)
[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:170713
[St] Status:MEDLINE


  8 / 11638 MEDLINE  
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[PMID]:28667050
[Au] Autor:Jackson WF; Boerman EM
[Ad] Endereço:Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan jacks783@msu.edu.
[Ti] Título:Regional heterogeneity in the mechanisms of myogenic tone in hamster arterioles.
[So] Source:Am J Physiol Heart Circ Physiol;313(3):H667-H675, 2017 Sep 01.
[Is] ISSN:1522-1539
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Myogenic tone is an important feature of arterioles and resistance arteries, but the mechanisms responsible for this hallmark characteristic remain unclear. We used pharmacological inhibitors to compare the roles played by phospholipase C (PLC; 10 µM U73122), inositol 1,4,5-trisphosphate receptors (IP Rs; 100 µM 2-aminoethoxydiphenylborane), protein kinase C (10 µM bisindolylmaleimide I), angiotensin II type 1 receptors (1 µM losartan), Rho kinase (10 nM-30 µM Y27632 or 300 nM H1152), stretch-activated ion channels (10 nM-1 µM Gd or 5 µM spider venom toxin GsMTx-4) and L-type voltage-gated Ca channels (0.3-100 µM diltiazem) in myogenic tone of cannulated, pressurized (80 cmH O), second-order hamster cremaster or cheek pouch arterioles. Effective inhibition of either PLC or IP Rs dilated cremaster arterioles, inhibited Ca waves, and reduced global Ca levels. In contrast, cheek pouch arterioles did not display Ca waves and inhibition of PLC or IP Rs had no effect on myogenic tone or intracellular Ca levels. Inhibition of Rho kinase dilated both cheek pouch and cremaster arterioles with equal efficacy and potency but also reduced intracellular Ca signals in both arterioles. Similarly, inhibition of mechanosensitive ion channels with Gd or GsMTx-4 produced comparable dilation in both arterioles. Inhibition of L-type Ca channels with diltiazem was more effective in dilating cremaster (86 ± 5% dilation, = 4) than cheek pouch arterioles (54 ± 4% dilation, = 6, < 0.05). Thus, there are substantial differences in the mechanisms underlying myogenic tone in hamster cremaster and cheek pouch arterioles. Regional heterogeneity in myogenic mechanisms could provide new targets for drug development to improve regional blood flow in a tissue-specific manner. Regional heterogeneity in the mechanisms of pressure-induced myogenic tone implies that resistance vessels may be able to alter myogenic signaling pathways to adapt to their environment. A better understanding of the spectrum of myogenic mechanisms could provide new targets to treat diseases that affect resistance artery and arteriolar function.
[Mh] Termos MeSH primário: Músculos Abdominais/irrigação sanguínea
Arteríolas/fisiologia
Sinalização do Cálcio
Bochecha/irrigação sanguínea
Mecanotransdução Celular
Vasoconstrição
Vasodilatação
[Mh] Termos MeSH secundário: Animais
Arteríolas/efeitos dos fármacos
Arteríolas/metabolismo
Pressão Sanguínea
Canais de Cálcio Tipo L/metabolismo
Sinalização do Cálcio/efeitos dos fármacos
Relação Dose-Resposta a Droga
Técnicas In Vitro
Receptores de Inositol 1,4,5-Trifosfato/metabolismo
Masculino
Mecanotransdução Celular/efeitos dos fármacos
Mesocricetus
Microcirculação
Especificidade de Órgãos
Proteína Quinase C/metabolismo
Fatores de Tempo
Fosfolipases Tipo C/metabolismo
Resistência Vascular
Vasoconstrição/efeitos dos fármacos
Vasoconstritores/farmacologia
Vasodilatação/efeitos dos fármacos
Vasodilatadores/farmacologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels, L-Type); 0 (Inositol 1,4,5-Trisphosphate Receptors); 0 (Vasoconstrictor Agents); 0 (Vasodilator Agents); EC 2.7.11.13 (Protein Kinase C); EC 3.1.4.- (Type C Phospholipases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170702
[St] Status:MEDLINE
[do] DOI:10.1152/ajpheart.00183.2017


  9 / 11638 MEDLINE  
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[PMID]:28584054
[Au] Autor:Sleno R; Devost D; Pétrin D; Zhang A; Bourque K; Shinjo Y; Aoki J; Inoue A; Hébert TE
[Ad] Endereço:From the Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec H3G 1Y6, Canada.
[Ti] Título:Conformational biosensors reveal allosteric interactions between heterodimeric AT1 angiotensin and prostaglandin F2α receptors.
[So] Source:J Biol Chem;292(29):12139-12152, 2017 Jul 21.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:G protein-coupled receptors (GPCRs) are conformationally dynamic proteins transmitting ligand-encoded signals in multiple ways. This transmission is highly complex and achieved through induction of distinct GPCR conformations, which preferentially drive specific receptor-mediated signaling events. This conformational capacity can be further enlarged via allosteric effects between dimers, warranting further study of these effects. Using GPCR conformation-sensitive biosensors, we investigated allosterically induced conformational changes in the recently reported F prostanoid (FP)/angiotensin II type 1 receptor (AT1R) heterodimer. Ligand occupancy of the AT1R induced distinct conformational changes in FP compared with those driven by PGF2α in bioluminescence resonance energy transfer (BRET)-based FP biosensors engineered with luciferase (RLuc) as an energy donor in the C-tail and fluorescein arsenical hairpin binder (FlAsH)-labeled acceptors at different positions in the intracellular loops. We also found that this allosteric communication is mediated through Gα and may also involve proximal (phospholipase C) but not distal (protein kinase C) signaling partners. Interestingly, ß-arrestin-biased AT1R agonists could also transmit a Gα -dependent signal to FP without activation of downstream Gα signaling. This transmission of information was specific to the AT1R/FP complex, as activation of Gα by the oxytocin receptor did not recapitulate the same phenomenon. Finally, information flow was asymmetric in the sense that FP activation had negligible effects on AT1R-based conformational biosensors. The identification of partner-induced GPCR conformations may help identify novel allosteric effects when investigating multiprotein receptor signaling complexes.
[Mh] Termos MeSH primário: Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo
Modelos Moleculares
Receptor Tipo 1 de Angiotensina/metabolismo
Receptores de Prostaglandina/metabolismo
Transdução de Sinais
Fosfolipases Tipo C/metabolismo
[Mh] Termos MeSH secundário: Regulação Alostérica
Técnicas de Transferência de Energia por Ressonância de Bioluminescência
Técnicas Biossensoriais
Membrana Celular/metabolismo
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/química
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética
Células HEK293
Seres Humanos
Ligantes
Luciferases de Renilla/química
Luciferases de Renilla/genética
Luciferases de Renilla/metabolismo
Oligopeptídeos/genética
Oligopeptídeos/metabolismo
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
Proteína Quinase C/metabolismo
Multimerização Proteica
Receptor Tipo 1 de Angiotensina/agonistas
Receptor Tipo 1 de Angiotensina/química
Receptor Tipo 1 de Angiotensina/genética
Receptores de Ocitocina/agonistas
Receptores de Ocitocina/química
Receptores de Ocitocina/genética
Receptores de Ocitocina/metabolismo
Receptores de Prostaglandina/agonistas
Receptores de Prostaglandina/química
Receptores de Prostaglandina/genética
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AGTR1 protein, human); 0 (GNAQ protein, human); 0 (Ligands); 0 (OXTR protein, human); 0 (Oligopeptides); 0 (Peptide Fragments); 0 (Receptor, Angiotensin, Type 1); 0 (Receptors, Oxytocin); 0 (Receptors, Prostaglandin); 0 (Recombinant Fusion Proteins); 0 (prostaglandin F2alpha receptor); 98849-88-8 (FLAG peptide); EC 1.13.12.5 (Luciferases, Renilla); EC 2.7.11.13 (Protein Kinase C); EC 3.1.4.- (Type C Phospholipases); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
[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:170607
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.793877


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[PMID]:28575023
[Au] Autor:Turku A; Rinne MK; Boije Af Gennäs G; Xhaard H; Lindholm D; Kukkonen JP
[Ad] Endereço:Biochemistry and Cell Biology, Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
[Ti] Título:Orexin receptor agonist Yan 7874 is a weak agonist of orexin/hypocretin receptors and shows orexin receptor-independent cytotoxicity.
[So] Source:PLoS One;12(6):e0178526, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Two promising lead structures of small molecular orexin receptor agonist have been reported, but without detailed analyses of the pharmacological properties. One of them, 1-(3,4-dichlorophenyl)-2-[2-imino-3-(4-methylbenzyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl]ethan-1-ol (Yan 7874), is commercially available, and we set out to analyze its properties. As test system we utilized human OX1 and OX2 orexin receptor-expressing Chinese hamster ovary (CHO) K1 cells as well as control CHO-K1 and neuro-2a neuroblastoma cells. Gq-coupling was assessed by measurement of intracellular Ca2+ and phospholipase C activity, and the coupling to Gi and Gs by adenylyl cyclase inhibition and stimulation, respectively. At concentrations above 1 µM, strong Ca2+ and low phospholipase C responses to Yan 7874 were observed in both OX1- and OX2-expressing cells. However, a major fraction of the response was not mediated by orexin receptors, as determined utilizing the non-selective orexin receptor antagonist N-biphenyl-2-yl-1-{[(1-methyl-1H-benzimidazol-2-yl)sulfanyl]acetyl}-L-prolinamide (TCS 1102) as well as control CHO-K1 cells. Yan 7874 did not produce any specific adenylyl cyclase response. Some experiments suggested an effect on cell viability by Yan 7874, and we thus analyzed this. Within a few hours of exposure, Yan 7874 markedly changed cell morphology (shrunken, rich in vacuoles), reduced growth, promoted cell detachment, and induced necrotic cell death. The effect was equal in cells expressing orexin receptors or not. Thus, Yan 7874 is a weak partial agonist of orexin receptors. It also displays strong off-target effects in the same concentration range, culminating in necrotic cell demise. This makes Yan 7874 unsuitable as orexin receptor agonist.
[Mh] Termos MeSH primário: Benzimidazóis/farmacologia
Iminas/farmacologia
Receptores de Orexina/agonistas
[Mh] Termos MeSH secundário: Adenilil Ciclases/metabolismo
Animais
Células CHO
Cálcio/metabolismo
Morte Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Cricetinae
Cricetulus
Seres Humanos
Fosfolipases Tipo C/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-(3,4-dichlorophenyl)-2-(2-imino-3-(4-methylbenzyl)-2,3-dihydro-1H-benzo(d)imidazol-1-yl)ethan-1-ol); 0 (Benzimidazoles); 0 (Imines); 0 (Orexin Receptors); EC 3.1.4.- (Type C Phospholipases); EC 4.6.1.1 (Adenylyl Cyclases); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178526



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