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[PMID]:28460635
[Au] Autor:Chen I; Mathews-Greiner L; Li D; Abisoye-Ogunniyan A; Ray S; Bian Y; Shukla V; Zhang X; Guha R; Thomas C; Gryder B; Zacharia A; Beane JD; Ravichandran S; Ferrer M; Rudloff U
[Ad] Endereço:Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes for Health, CCR 4 West/4-3740, 10 Center Drive, Bethesda, MD, 20892-0001, USA.
[Ti] Título:Transcriptomic profiling and quantitative high-throughput (qHTS) drug screening of CDH1 deficient hereditary diffuse gastric cancer (HDGC) cells identify treatment leads for familial gastric cancer.
[So] Source:J Transl Med;15(1):92, 2017 May 01.
[Is] ISSN:1479-5876
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Patients with hereditary diffuse gastric cancer (HDGC), a cancer predisposition syndrome associated with germline mutations of the CDH1 (E-cadherin) gene, have few effective treatment options. Despite marked differences in natural history, histopathology, and genetic profile to patients afflicted by sporadic gastric cancer, patients with HDGC receive, in large, identical systemic regimens. The lack of a robust preclinical in vitro system suitable for effective drug screening has been one of the obstacles to date which has hampered therapeutic advances in this rare disease. METHODS: In order to identify therapeutic leads selective for the HDGC subtype of gastric cancer, we compared gene expression profiles and drug phenotype derived from an oncology library of 1912 compounds between gastric cancer cells established from a patient with metastatic HDGC harboring a c.1380delA CDH1 germline variant and sporadic gastric cancer cells. RESULTS: Unsupervised hierarchical cluster analysis shows select gene expression alterations in c.1380delA CDH1 SB.mhdgc-1 cells compared to a panel of sporadic gastric cancer cell lines with enrichment of ERK1-ERK2 (extracellular signal regulated kinase) and IP3 (inositol trisphosphate)/DAG (diacylglycerol) signaling as the top networks in c.1380delA SB.mhdgc-1 cells. Intracellular phosphatidylinositol intermediaries were increased upon direct measure in c.1380delA CDH1 SB.mhdgc-1 cells. Differential high-throughput drug screening of c.1380delA CDH1 SB.mhdgc-1 versus sporadic gastric cancer cells identified several compound classes with enriched activity in c.1380 CDH1 SB.mhdgc-1 cells including mTOR (Mammalian Target Of Rapamycin), MEK (Mitogen-Activated Protein Kinase), c-Src kinase, FAK (Focal Adhesion Kinase), PKC (Protein Kinase C), or TOPO2 (Topoisomerase II) inhibitors. Upon additional drug response testing, dual PI3K (Phosphatidylinositol 3-Kinase)/mTOR and topoisomerase 2A inhibitors displayed up to >100-fold increased activity in hereditary c.1380delA CDH1 gastric cancer cells inducing apoptosis most effectively in cells with deficient CDH1 function. CONCLUSION: Integrated pharmacological and transcriptomic profiling of hereditary diffuse gastric cancer cells with a loss-of-function c.1380delA CDH1 mutation implies various pharmacological vulnerabilities selective to CDH1-deficient familial gastric cancer cells and suggests novel treatment leads for future preclinical and clinical treatment studies of familial gastric cancer.
[Mh] Termos MeSH primário: Caderinas/deficiência
Avaliação Pré-Clínica de Medicamentos
Perfilação da Expressão Gênica
Ensaios de Triagem em Larga Escala
Neoplasias Gástricas/tratamento farmacológico
Neoplasias Gástricas/genética
[Mh] Termos MeSH secundário: Adulto
Caderinas/genética
Linhagem Celular Tumoral
Diglicerídeos/metabolismo
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Feminino
Regulação Neoplásica da Expressão Gênica
Predisposição Genética para Doença
Mutação em Linhagem Germinativa/genética
Seres Humanos
Fosfatos de Inositol/metabolismo
Masculino
Linhagem
Reprodutibilidade dos Testes
Neoplasias Gástricas/patologia
Regulação para Cima/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CDH1 protein, human); 0 (Cadherins); 0 (Diglycerides); 0 (Inositol Phosphates); 0 (inositol 3,4,5-trisphosphate); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1186/s12967-017-1197-5


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[PMID]:28450399
[Au] Autor:Franco-Echevarría E; Sanz-Aparicio J; Brearley CA; González-Rubio JM; González B
[Ad] Endereço:From the Departamento de Cristalografía y Biología Estructural, Instituto de Química-Física "Rocasolano," Consejo Superior de Investigaciones Científicas, Serrano 119, 28006 Madrid, Spain and.
[Ti] Título:The crystal structure of mammalian inositol 1,3,4,5,6-pentakisphosphate 2-kinase reveals a new zinc-binding site and key features for protein function.
[So] Source:J Biol Chem;292(25):10534-10548, 2017 06 23.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inositol 1,3,4,5,6-pentakisphosphate 2-kinases (IP 2-Ks) are part of a family of enzymes in charge of synthesizing inositol hexakisphosphate (IP ) in eukaryotic cells. This protein and its product IP present many roles in cells, participating in mRNA export, embryonic development, and apoptosis. We reported previously that the full-length IP 2-K from is a zinc metallo-enzyme, including two separated lobes (the N- and C-lobes). We have also shown conformational changes in IP 2-K and have identified the residues involved in substrate recognition and catalysis. However, the specific features of mammalian IP 2-Ks remain unknown. To this end, we report here the first structure for a murine IP 2-K in complex with ATP/IP or IP Our structural findings indicated that the general folding in N- and C-lobes is conserved with IP 2-K. A helical scaffold in the C-lobe constitutes the inositol phosphate-binding site, which, along with the participation of the N-lobe, endows high specificity to this protein. However, we also noted large structural differences between the orthologues from these two eukaryotic kingdoms. These differences include a novel zinc-binding site and regions unique to the mammalian IP 2-K, as an unexpected basic patch on the protein surface. In conclusion, our findings have uncovered distinct features of a mammalian IP 2-K and set the stage for investigations into protein-protein or protein-RNA interactions important for IP 2-K function and activity.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/química
Fosfatos de Inositol/química
Fosfotransferases (Aceptor do Grupo Fosfato)/química
[Mh] Termos MeSH secundário: Animais
Arabidopsis/enzimologia
Proteínas de Arabidopsis/química
Sítios de Ligação
Cristalografia por Raios X
Camundongos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Arabidopsis Proteins); 0 (Inositol Phosphates); 8L70Q75FXE (Adenosine Triphosphate); EC 2.7.4.- (Phosphotransferases (Phosphate Group Acceptor)); EC 2.7.4.21 (inositol hexakisphosphate kinase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.780395


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[PMID]:28742687
[Au] Autor:Limani P; Linecker M; Schneider MA; Kron P; Tschuor C; Kachaylo E; Ungethuem U; Nicolau C; Lehn JM; Graf R; Humar B; Clavien PA
[Ad] Endereço:*Department of Surgery and Transplantation, Swiss Hepato-pancreato-biliary (HPB) and Transplantation Laboratory, University Hospital Zurich, Zurich, Switzerland †Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA ‡Institute of Supramolecular Science and Engineering, University of Strasbourg, Strasbourg, France.
[Ti] Título:The Allosteric Hemoglobin Effector ITPP Inhibits Metastatic Colon Cancer in Mice.
[So] Source:Ann Surg;266(5):746-753, 2017 11.
[Is] ISSN:1528-1140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To test the effects of enhanced intracellular oxygen contents on the metastatic potential of colon cancer. BACKGROUND: Colorectal cancer is the commonest gastrointestinal carcinoma. Distant metastases occur in half of patients and are responsible for most cancer-related deaths. Tumor hypoxia is central to the pathogenesis of metastases. Myo-Inositoltrispyrophosphate (ITPP), a nontoxic, antihypoxic compound, has recently shown significant benefits in experimental cancer, particularly when combined with standard chemotherapy. Whether ITPP protects from distant metastases in primary colon cancer is unknown. METHODS: ITPP alone or combined with FOLFOX was tested in a mouse model with cecal implantation of green fluorescent protein-labeled syngeneic colorectal cancer cells. Tumor development was monitored through longitudinal magnetic resonance imaging-based morphometric analysis and survival. Established serum markers of tumor spread were measured serially and circulating tumor cells were detected via fluorescence measurements. RESULTS: ITPP significantly reduced the occurrence of metastases as well as other indicators of tumor aggressiveness. Less circulating tumor cells along with reduction in malignant serum markers (osteopontin, Cxcl12) were noted. The ITPP benefits also affected the primary cancer site. Importantly, animals treated with ITPP had a significant survival benefit compared with respective controls, while a combination of FOLFOX with ITPP conferred the maximum benefits, including dramatic improvements in survival (mean 86 vs 188 d). CONCLUSIONS: Restoring oxygen in metastatic colon cancer through ITPP inhibits tumor spread and markedly improves animal survival; an effect that is enhanced through the application of subsequent chemotherapy. These promising novel findings call for a clinical trial on ITPP in patients with colorectal cancer, which is under way.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Neoplasias do Colo/tratamento farmacológico
Neoplasias do Colo/patologia
Fosfatos de Inositol/uso terapêutico
Neoplasias Hepáticas/prevenção & controle
Neoplasias Hepáticas/secundário
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Biomarcadores Tumorais/sangue
Neoplasias do Colo/sangue
Neoplasias do Colo/mortalidade
Ensaio de Imunoadsorção Enzimática
Fluoruracila/uso terapêutico
Imuno-Histoquímica
Fosfatos de Inositol/farmacologia
Leucovorina/uso terapêutico
Neoplasias Hepáticas/sangue
Camundongos
Camundongos Endogâmicos C57BL
Células Neoplásicas Circulantes/efeitos dos fármacos
Compostos Organoplatínicos/uso terapêutico
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (Inositol Phosphates); 0 (Organoplatinum Compounds); 0 (inositol trispyrophosphate); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171214
[Lr] Data última revisão:
171214
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1097/SLA.0000000000002431


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[PMID]:27776974
[Au] Autor:Shears SB; Baughman BM; Gu C; Nair VS; Wang H
[Ad] Endereço:Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, 101 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA. Electronic address: shears@niehs.nih.gov.
[Ti] Título:The significance of the 1-kinase/1-phosphatase activities of the PPIP5K family.
[So] Source:Adv Biol Regul;63:98-106, 2017 Jan.
[Is] ISSN:2212-4934
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The inositol pyrophosphates (diphosphoinositol polyphosphates), which include 1-InsP , 5-InsP , and InsP , are highly 'energetic' signaling molecules that play important roles in many cellular processes, particularly with regards to phosphate and bioenergetic homeostasis. Two classes of kinases synthesize the PP-InsPs: IP6Ks and PPIP5Ks. The significance of the IP6Ks - and their 5-InsP product - has been widely reported. However, relatively little is known about the biological significance of the PPIP5Ks. The purpose of this review is to provide an update on developments in our understanding of key features of the PPIP5Ks, which we believe strengthens the hypothesis that their catalytic activities serve important cellular functions. Central to this discussion is the recent discovery that the PPIP5K is a rare example of a single protein that catalyzes a kinase/phosphatase futile cycle.
[Mh] Termos MeSH primário: Hidrolases Anidrido Ácido/metabolismo
Fosfatos de Inositol/metabolismo
Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo
Ácido Fítico/metabolismo
[Mh] Termos MeSH secundário: Hidrolases Anidrido Ácido/genética
Motivos de Aminoácidos
Metabolismo Energético/genética
Regulação da Expressão Gênica
Seres Humanos
Fosfotransferases (Aceptor do Grupo Fosfato)/química
Fosfotransferases (Aceptor do Grupo Fosfato)/genética
Domínios Proteicos
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Inositol Phosphates); 0 (inositol heptakisphosphate); 7IGF0S7R8I (Phytic Acid); EC 2.7.4.- (Phosphotransferases (Phosphate Group Acceptor)); EC 2.7.4.21 (PPIP5K1 protein, human); EC 3.6.- (Acid Anhydride Hydrolases); EC 3.6.1.- (diphosphoinositol polyphosphate phosphohydrolase)
[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:161026
[St] Status:MEDLINE


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[PMID]:28848052
[Au] Autor:Bruder LM; Gruninger RJ; Cleland CP; Mosimann SC
[Ad] Endereço:From the Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge AB T1K 3M4, Canada and.
[Ti] Título:Bacterial PhyA protein-tyrosine phosphatase-like -inositol phosphatases in complex with the Ins(1,3,4,5)P and Ins(1,4,5)P second messengers.
[So] Source:J Biol Chem;292(42):17302-17311, 2017 Oct 20.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:-Inositol phosphates (IPs) are important bioactive molecules that have multiple activities within eukaryotic cells, including well-known roles as second messengers and cofactors that help regulate diverse biochemical processes such as transcription and hormone receptor activity. Despite the typical absence of IPs in prokaryotes, many of these organisms express IPases (or phytases) that dephosphorylate IPs. Functionally, these enzymes participate in phosphate-scavenging pathways and in plant pathogenesis. Here, we determined the X-ray crystallographic structures of two catalytically inactive mutants of protein-tyrosine phosphatase-like -inositol phosphatases (PTPLPs) from the non-pathogenic bacteria (PhyAsr) and (PhyAmm) in complex with the known eukaryotic second messengers Ins(1,3,4,5)P and Ins(1,4,5)P Both enzymes bound these less-phosphorylated IPs in a catalytically competent manner, suggesting that IP hydrolysis has a role in plant pathogenesis. The less-phosphorylated IP binding differed in both the -inositol ring position and orientation when compared with a previously determined complex structure in the presence of -inositol-1,2,3,4,5,6-hexa phosphate (InsP or phytate). Further, we have demonstrated that PhyAsr and PhyAmm have different specificities for Ins(1,2,4,5,6)P , have identified structural features that account for this difference, and have shown that the absence of these features results in a broad specificity toward Ins(1,2,4,5,6)P These features are main-chain conformational differences in loops adjacent to the active site that include the extended loop prior to the penultimate helix, the extended Ω-loop, and a ß-hairpin turn of the Phy-specific domain.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Inositol 1,4,5-Trifosfato/química
Fosfatos de Inositol/química
Proteínas Tirosina Fosfatases/química
Sistemas do Segundo Mensageiro
Selenomonas/enzimologia
[Mh] Termos MeSH secundário: Cristalografia por Raios X
Estrutura Secundária de Proteína
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Inositol Phosphates); 25663-09-6 (inositol pentaphosphate); 85166-31-0 (Inositol 1,4,5-Trisphosphate); EC 3.1.3.48 (Protein Tyrosine Phosphatases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170830
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.787853


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[PMID]:28800362
[Au] Autor:Jiang P; Xing F; Guo B; Yang J; Li Z; Wei W; Hu F; Lee I; Zhang X; Pan L; Xu J
[Ad] Endereço:The Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, TEDA Institute of Applied Physics and School of Physics, Nankai University, Tianjin, China.
[Ti] Título:Nucleotide transmitters ATP and ADP mediate intercellular calcium wave communication via P2Y12/13 receptors among BV-2 microglia.
[So] Source:PLoS One;12(8):e0183114, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nerve injury is accompanied by a liberation of diverse nucleotides, some of which act as 'find/eat-me' signals in mediating neuron-glial interplay. Intercellular Ca2+ wave (ICW) communication is the main approach by which glial cells interact and coordinate with each other to execute immune defense. However, the detailed mechanisms on how these nucleotides participate in ICW communication remain largely unclear. In the present work, we employed a mechanical stimulus to an individual BV-2 microglia to simulate localized injury. Remarkable ICW propagation was observed no matter whether calcium was in the environment or not. Apyrase (ATP/ADP-hydrolyzing enzyme), suramin (broad-spectrum P2 receptor antagonist), 2-APB (IP3 receptor blocker) and thapsigargin (endoplasmic reticulum calcium pump inhibitor) potently inhibited these ICWs, respectively, indicating the dependence of nucleotide signals and P2Y receptors. Then, we detected the involvement of five naturally occurring nucleotides (ATP, ADP, UTP, UDP and UDP-glucose) by desensitizing receptors. Results showed that desensitization with ATP and ADP could block ICW propagation in a dose-dependent manner, whereas other nucleotides had little effect. Meanwhile, the expression of P2Y receptors in BV-2 microglia was identified and their contributions were analyzed, from which we suggested P2Y12/13 receptors activation mostly contributed to ICWs. Besides, we estimated that extracellular ATP and ADP concentration sensed by BV-2 microglia was about 0.3 µM during ICWs by analyzing calcium dynamic characteristics. Taken together, these results demonstrated that the nucleotides ATP and ADP were predominant signal transmitters in mechanical stimulation-induced ICW communication through acting on P2Y12/13 receptors in BV-2 microglia.
[Mh] Termos MeSH primário: Difosfato de Adenosina/metabolismo
Trifosfato de Adenosina/metabolismo
Cálcio/metabolismo
Microglia/metabolismo
Receptores Purinérgicos P2Y12/metabolismo
Receptores Purinérgicos P2/metabolismo
[Mh] Termos MeSH secundário: Animais
Apirase/farmacologia
Fenômenos Biomecânicos
Compostos de Boro/farmacologia
Sinalização do Cálcio/efeitos dos fármacos
Comunicação Celular/efeitos dos fármacos
Linhagem Celular Transformada
Expressão Gênica
Fosfatos de Inositol/farmacologia
Mecanotransdução Celular/efeitos dos fármacos
Camundongos
Microglia/citologia
Microglia/efeitos dos fármacos
Imagem Molecular
Receptores Purinérgicos P2/genética
Receptores Purinérgicos P2Y12/genética
Suramina/farmacologia
Tapsigargina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-aminoethyl diphenylborinate); 0 (Boron Compounds); 0 (Inositol Phosphates); 0 (P2ry12 protein, mouse); 0 (P2ry13 protein, mouse); 0 (Receptors, Purinergic P2); 0 (Receptors, Purinergic P2Y12); 2831-74-5 (inositol 3-phosphate); 6032D45BEM (Suramin); 61D2G4IYVH (Adenosine Diphosphate); 67526-95-8 (Thapsigargin); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.1.5 (Apyrase); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170812
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183114


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[PMID]:28629791
[Au] Autor:Xie N; Ruprich-Robert G; Chapeland-Leclerc F; Coppin E; Lalucque H; Brun S; Debuchy R; Silar P
[Ad] Endereço:Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China; Univ Paris Diderot, Sorbonne Paris Cité, Laboratoire Interdisciplinaire des Energies de Demain, 75205 Paris Cedex 13, France.
[Ti] Título:Inositol-phosphate signaling as mediator for growth and sexual reproduction in Podospora anserina.
[So] Source:Dev Biol;429(1):285-305, 2017 09 01.
[Is] ISSN:1095-564X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The molecular pathways involved in the development of multicellular fruiting bodies in fungi are still not well known. Especially, the interplay between the mycelium, the female tissues and the zygotic tissues of the fruiting bodies is poorly documented. Here, we describe PM154, a new strain of the model ascomycetes Podospora anserina able to mate with itself and that enabled the easy recovery of new mutants affected in fruiting body development. By complete genome sequencing of spod1, one of the new mutants, we identified an inositol phosphate polykinase gene as essential, especially for fruiting body development. A factor present in the wild type and diffusible in mutant hyphae was able to induce the development of the maternal tissues of the fruiting body in spod1, but failed to promote complete development of the zygotic ones. Addition of myo-inositol in the growth medium was able to increase the number of developing fruiting bodies in the wild type, but not in spod1. Overall, the data indicated that inositol and inositol polyphosphates were involved in promoting fruiting body maturation, but also in regulating the number of fruiting bodies that developed after fertilization. The same effect of inositol was seen in two other fungi, Sordaria macrospora and Chaetomium globosum. Key role of the inositol polyphosphate pathway during fruiting body maturation appears thus conserved during the evolution of Sordariales fungi.
[Mh] Termos MeSH primário: Fosfatos de Inositol/metabolismo
Podospora/crescimento & desenvolvimento
Podospora/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Núcleo Celular/metabolismo
Fertilidade
Carpóforos/metabolismo
Proteínas Fúngicas/química
Proteínas Fúngicas/metabolismo
Genes Fúngicos
Proteínas de Fluorescência Verde/metabolismo
Inositol/metabolismo
Sistema de Sinalização das MAP Quinases
Mosaicismo
Mutação/genética
Fenótipo
Pigmentos Biológicos/metabolismo
Podospora/enzimologia
Podospora/genética
Transporte Proteico
Reprodução
Sordariales/metabolismo
Esporos Fúngicos/metabolismo
Temperatura Ambiente
Zigoto/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fungal Proteins); 0 (Inositol Phosphates); 0 (Pigments, Biological); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); 4L6452S749 (Inositol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE


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[PMID]:28600357
[Au] Autor:Vessichelli M; Mariggiò S; Varone A; Zizza P; Di Santo A; Amore C; Dell'Elba G; Cutignano A; Fontana A; Cacciapuoti C; Di Costanzo G; Zannini M; de Cristofaro T; Evangelista V; Corda D
[Ad] Endereço:From the Institute of Protein Biochemistry, National Research Council, Via P. Castellino 111, 80131 Naples, Italy.
[Ti] Título:The natural phosphoinositide derivative glycerophosphoinositol inhibits the lipopolysaccharide-induced inflammatory and thrombotic responses.
[So] Source:J Biol Chem;292(31):12828-12841, 2017 Aug 04.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inflammatory responses are elicited through lipid products of phospholipase A activity that acts on the membrane phospholipids, including the phosphoinositides, to form the proinflammatory arachidonic acid and, in parallel, the glycerophosphoinositols. Here, we investigate the role of the glycerophosphoinositol in the inflammatory response. We show that it is part of a negative feedback loop that limits proinflammatory and prothrombotic responses in human monocytes stimulated with lipopolysaccharide. This inhibition is exerted both on the signaling cascade initiated by the lipopolysaccharide with the glycerophosphoinositol-dependent decrease in IκB kinase α/ß, p38, JNK, and Erk1/2 kinase phosphorylation and at the nuclear level with decreased NF-κB translocation and binding to inflammatory gene promoters. In a model of endotoxemia in the mouse, treatment with glycerophosphoinositol reduced TNF-α synthesis, which supports the concept that glycerophosphoinositol inhibits the synthesis of proinflammatory and prothrombotic compounds and might thus have a role as an endogenous mediator in the resolution of inflammation. As indicated, this effect of glycerophosphoinositol can also be exploited in the treatment of manifestations of severe inflammation by exogenous administration of the compound.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/uso terapêutico
Coagulação Sanguínea/efeitos dos fármacos
Endotoxemia/tratamento farmacológico
Regulação da Expressão Gênica/efeitos dos fármacos
Fosfatos de Inositol/uso terapêutico
Monócitos/efeitos dos fármacos
Processamento de Proteína Pós-Traducional/efeitos dos fármacos
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular/efeitos dos fármacos
Animais
Anti-Inflamatórios não Esteroides/farmacologia
Anticoagulantes/farmacologia
Anticoagulantes/uso terapêutico
Biomarcadores/sangue
Biomarcadores/metabolismo
Células Cultivadas
Imunoprecipitação da Cromatina
Relação Dose-Resposta a Droga
Endotoxemia/imunologia
Endotoxemia/metabolismo
Células HeLa
Seres Humanos
Fosfatos de Inositol/farmacologia
Lipopolissacarídeos/antagonistas & inibidores
Lipopolissacarídeos/toxicidade
Masculino
Camundongos Endogâmicos C57BL
Microscopia Confocal
Monócitos/citologia
Monócitos/imunologia
Monócitos/metabolismo
NF-kappa B/antagonistas & inibidores
NF-kappa B/sangue
NF-kappa B/metabolismo
Fosforilação/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Anticoagulants); 0 (Biomarkers); 0 (Inositol Phosphates); 0 (Lipopolysaccharides); 0 (NF-kappa B); 16824-65-0 (glycerylphosphoinositol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170611
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.773861


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[PMID]:28502771
[Au] Autor:Li S; Sullivan NL; Rouphael N; Yu T; Banton S; Maddur MS; McCausland M; Chiu C; Canniff J; Dubey S; Liu K; Tran V; Hagan T; Duraisingham S; Wieland A; Mehta AK; Whitaker JA; Subramaniam S; Jones DP; Sette A; Vora K; Weinberg A; Mulligan MJ; Nakaya HI; Levin M; Ahmed R; Pulendran B
[Ad] Endereço:Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30303, USA.
[Ti] Título:Metabolic Phenotypes of Response to Vaccination in Humans.
[So] Source:Cell;169(5):862-877.e17, 2017 May 18.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4 T cells yet limited CD8 T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.
[Mh] Termos MeSH primário: Vacina contra Herpes Zoster/imunologia
[Mh] Termos MeSH secundário: Imunidade Adaptativa
Adulto
Idoso
Envelhecimento
Formação de Anticorpos
Linfócitos T CD4-Positivos/imunologia
Feminino
Citometria de Fluxo
Perfilação da Expressão Gênica
Redes Reguladoras de Genes
Seres Humanos
Fosfatos de Inositol/imunologia
Estudos Longitudinais
Masculino
Metabolômica
Meia-Idade
Caracteres Sexuais
Esteróis/metabolismo
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Herpes Zoster Vaccine); 0 (Inositol Phosphates); 0 (Sterols)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170715
[Lr] Data última revisão:
170715
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE


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[PMID]:28372252
[Au] Autor:Duong QH; Clark KD; Lapsley KG; Pegg RB
[Ad] Endereço:Department of Food Science & Technology, College of Agricultural and Environmental Sciences, The University of Georgia, 100 Cedar Street, Athens, GA 30602, USA.
[Ti] Título:Quantification of inositol phosphates in almond meal and almond brown skins by HPLC/ESI/MS.
[So] Source:Food Chem;229:84-92, 2017 Aug 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The extraction and measurement of all six forms of inositol phosphates (InsPs) in almond meal and brown skins were improved from existing methods by pH adjustment, supplementation of EDTA, and rapid analysis via anion-exchange high-performance liquid chromatography coupled with electrospray ionization mass spectrometry. The quantity of InsPs in six major almond cultivars ranged from 8 to 12µmol/g in the meal and 5 to 14µmol/g in the brown skins. InsP was the dominant form, but lower forms still accounted for ∼20% of the total InsPs molar concentration in a majority of the samples. InsPs contributed 32-55% of the organic phosphorus content and 20-38% of the total phosphorus content in the meal. In brown skins, these ranges were 44-77% and 30-52%, respectively. The successful application of this analytical method with almonds demonstrates its potential use for re-examination of the reported phytic acid contents in many other tree nuts, legumes, grains, and complex foods.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Suplementos Nutricionais/análise
Fosfatos de Inositol/química
Prunus dulcis/química
Espectrometria de Massas por Ionização por Electrospray/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Inositol Phosphates)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170505
[Lr] Data última revisão:
170505
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE



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