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[PMID]:29429505
[Au] Autor:Seneschal J
[Ad] Endereço:Centre de référence des maladies rares de la peau, hôpital Saint-André, CHU de Bordeaux, BMGIC, INSERM U1035, équipe immunodermatologie ATIP-AVENIR, France. Electronic address: julien.seneschal@chu-bordeaux.fr.
[Ti] Título:[What's new in dermatological research?]
[Ti] Título:Quoi de neuf en recherche dermatologique ?.
[So] Source:Ann Dermatol Venereol;143 Suppl 3:S19-S22, 2016 Dec.
[Is] ISSN:0151-9638
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:Many research studies dedicated to skin have been published in 2016 in high impact factor journals. This article summarises a selection of research works published between December 2015 and September 2016. New insights into the understanding of the mechanisms involved in psoriasis and atopic dermatitis can lead to better management of these chronic inflammatory disorders. Moreover, a better understanding of the relation between the host and the environment could lead to new therapeutic strategies. Finally, new devices first dedicated to skin inflammatory diseases have been developed with success that could be extended to other chronic inflammatory disorders.
[Mh] Termos MeSH primário: Dermatopatias
[Mh] Termos MeSH secundário: Animais
Reabsorção Óssea/fisiopatologia
Dermatologia
Engenharia Genética
Terapia Genética
Seres Humanos
Inflamação/fisiopatologia
Mordeduras e Picadas de Insetos/imunologia
Janus Quinase 3/antagonistas & inibidores
Microbiota
Inibidores de Proteínas Quinases/uso terapêutico
Dermatopatias/diagnóstico
Dermatopatias/imunologia
Dermatopatias/terapia
Venenos de Aranha/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); 0 (Spider Venoms); EC 2.7.10.2 (Janus Kinase 3)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE


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[PMID]:28880874
[Au] Autor:Sousa SR; Wingerd JS; Brust A; Bladen C; Ragnarsson L; Herzig V; Deuis JR; Dutertre S; Vetter I; Zamponi GW; King GF; Alewood PF; Lewis RJ
[Ad] Endereço:IMB Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
[Ti] Título:Discovery and mode of action of a novel analgesic ß-toxin from the African spider Ceratogyrus darlingi.
[So] Source:PLoS One;12(9):e0182848, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Spider venoms are rich sources of peptidic ion channel modulators with important therapeutical potential. We screened a panel of 60 spider venoms to find modulators of ion channels involved in pain transmission. We isolated, synthesized and pharmacologically characterized Cd1a, a novel peptide from the venom of the spider Ceratogyrus darlingi. Cd1a reversibly paralysed sheep blowflies (PD50 of 1318 pmol/g) and inhibited human Cav2.2 (IC50 2.6 µM) but not Cav1.3 or Cav3.1 (IC50 > 30 µM) in fluorimetric assays. In patch-clamp electrophysiological assays Cd1a inhibited rat Cav2.2 with similar potency (IC50 3 µM) without influencing the voltage dependence of Cav2.2 activation gating, suggesting that Cd1a doesn't act on Cav2.2 as a classical gating modifier toxin. The Cd1a binding site on Cav2.2 did not overlap with that of the pore blocker ω-conotoxin GVIA, but its activity at Cav2.2-mutant indicated that Cd1a shares some molecular determinants with GVIA and MVIIA, localized near the pore region. Cd1a also inhibited human Nav1.1-1.2 and Nav1.7-1.8 (IC50 0.1-6.9 µM) but not Nav1.3-1.6 (IC50 > 30 µM) in fluorimetric assays. In patch-clamp assays, Cd1a strongly inhibited human Nav1.7 (IC50 16 nM) and produced a 29 mV depolarising shift in Nav1.7 voltage dependence of activation. Cd1a (400 pmol) fully reversed Nav1.7-evoked pain behaviours in mice without producing side effects. In conclusion, Cd1a inhibited two anti-nociceptive targets, appearing to interfere with Cav2.2 inactivation gating, associated with the Cav2.2 α-subunit pore, while altering the activation gating of Nav1.7. Cd1a was inactive at some of the Nav and Cav channels expressed in skeletal and cardiac muscles and nodes of Ranvier, apparently contributing to the lack of side effects at efficacious doses, and suggesting potential as a lead for development of peripheral pain treatments.
[Mh] Termos MeSH primário: Analgésicos/farmacologia
Venenos de Aranha/química
Aranhas/química
[Mh] Termos MeSH secundário: Analgésicos/química
Animais
Sítios de Ligação/efeitos dos fármacos
Canais de Cálcio Tipo N/metabolismo
Eletrofisiologia
Fluorometria
Seres Humanos
Camundongos
Canal de Sódio Disparado por Voltagem NAV1.1/metabolismo
Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo
Peptídeos/química
Peptídeos/farmacologia
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics); 0 (Cacna1b protein, rat); 0 (Calcium Channels, N-Type); 0 (NAV1.1 Voltage-Gated Sodium Channel); 0 (NAV1.7 Voltage-Gated Sodium Channel); 0 (Peptides); 0 (Spider Venoms)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182848


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[PMID]:28645932
[Au] Autor:Rajamani R; Wu S; Rodrigo I; Gao M; Low S; Megson L; Wensel D; Pieschl RL; Post-Munson DJ; Watson J; Langley DR; Ahlijanian MK; Bristow LJ; Herrington J
[Ad] Endereço:Molecular Discovery Technologies, Wallingford, Connecticut, Princeton, New Jersey, and Waltham, Massachusetts (R.R., S.W., I.R., M.G., S.L., L.M., D.W., D.R.L.); Discovery Biology (R.L.P., D.J.P.-M., M.K.A., L.J.B., J.H.) and Lead Discovery and Optimization (J.W.), Bristol-Myers Squibb Company, Wall
[Ti] Título:A Functional Na 1.7-Na Ab Chimera with a Reconstituted High-Affinity ProTx-II Binding Site.
[So] Source:Mol Pharmacol;92(3):310-317, 2017 Sep.
[Is] ISSN:1521-0111
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Na 1.7 voltage-gated sodium channel is implicated in human pain perception by genetics. Rare gain of function mutations in Na 1.7 lead to spontaneous pain in humans whereas loss of function mutations results in congenital insensitivity to pain. Hence, agents that specifically modulate the function of Na 1.7 have the potential to yield novel therapeutics to treat pain. The complexity of the channel and the challenges to generate recombinant cell lines with high Na 1.7 expression have led to a surrogate target strategy approach employing chimeras with the bacterial channel Na Ab. In this report we describe the design, synthesis, purification, and characterization of a chimera containing part of the voltage sensor domain 2 (VSD2) of Na 1.7. Importantly, this chimera, DII S1-S4, forms functional sodium channels and is potently inhibited by the Na 1.7 VSD2 targeted peptide toxin ProTx-II. Further, we show by [ I]ProTx-II binding and surface plasmon resonance that the purified DII S1-S4 protein retains high affinity ProTx-II binding in detergent. We employed the purified DII S1-S4 protein to create a scintillation proximity assay suitable for high-throughput screening. The creation of a Na 1.7-Na Ab chimera with the VSD2 toxin binding site provides an important tool for the identification of novel Na 1.7 inhibitors and for structural studies to understand the toxin-channel interaction.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Canal de Sódio Disparado por Voltagem NAV1.7/fisiologia
Proteínas Recombinantes de Fusão/química
Venenos de Aranha/metabolismo
Canais de Sódio Disparados por Voltagem/química
[Mh] Termos MeSH secundário: Proteínas de Bactérias/fisiologia
Sítios de Ligação
Células HEK293
Seres Humanos
Ressonância de Plasmônio de Superfície
Canais de Sódio Disparados por Voltagem/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (NAV1.7 Voltage-Gated Sodium Channel); 0 (ProTx-II peptide); 0 (Recombinant Fusion Proteins); 0 (Spider Venoms); 0 (Voltage-Gated Sodium Channels)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170625
[St] Status:MEDLINE
[do] DOI:10.1124/mol.117.108712


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[PMID]:28629730
[Au] Autor:Palhares MR; Silva JF; Rezende MJS; Santos DC; Silva-Junior CA; Borges MH; Ferreira J; Gomez MV; Castro-Junior CJ
[Ad] Endereço:Department of Neurotransmitters, Institute for Education and Research, Hospital Santa Casa, Belo Horizonte, Minas Gerais 30150-240, Brazil.
[Ti] Título:Synergistic antinociceptive effect of a calcium channel blocker and a TRPV1 blocker in an acute pain model in mice.
[So] Source:Life Sci;182:122-128, 2017 Aug 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Extensive evidence supports a role for voltage-gated calcium channels (VGCC) and TRPV1 receptors in pain transmission and modulation. We investigated the profile of analgesic interaction between Phα1ß toxin (a VGCC blocker) and SB366791 (selective TRPV1 antagonist) in a model of acute pain induced by capsaicin. Changes in body temperature induced by combination regimens were also evaluated. MAIN METHODS: Isobolographic approach with a fixed dose-ratio of combined drugs was used to determine whether antinociceptive interaction of Phα1ß and SB366791 are subadditive, additive or synergic. Body temperature was obtained by thermal infrared imaging. KEY FINDINGS: Phα1ß and SB366791 interact in a synergistic manner to cause antinociception. We found an interaction index (α) of 0.07 for Phα1ß and SB366791 when these drugs were injected together intraplantarly, which indicates that in vivo interaction between these drugs is greater than additive interaction. Synergism also occurred when intraplantar SB366791 was administered simultaneously with intrathecal Phα1ß (interaction index α=0.06) suggesting a 15 fold rise in potency on the analgesic effect of these drugs when they are added together. It was observed no significant alterations in body temperature of animals treated with this combination regimen. SIGNIFICANCE: Our data reveal that Phα1ß toxin potentiates in 15 fold the antinociceptive action of the TRPV1 blocker SB366791. Therefore, lower doses of these drugs are required to achieve antinociceptive effects when these agents are given in combination.
[Mh] Termos MeSH primário: Dor Aguda/tratamento farmacológico
Analgésicos/farmacologia
Anilidas/farmacologia
Cinamatos/farmacologia
Venenos de Aranha/farmacologia
Canais de Cátion TRPV/antagonistas & inibidores
[Mh] Termos MeSH secundário: Analgésicos/administração & dosagem
Anilidas/administração & dosagem
Animais
Temperatura Corporal
Bloqueadores dos Canais de Cálcio/administração & dosagem
Bloqueadores dos Canais de Cálcio/farmacologia
Capsaicina
Cinamatos/administração & dosagem
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Sinergismo Farmacológico
Camundongos
Venenos de Aranha/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics); 0 (Anilides); 0 (Calcium Channel Blockers); 0 (Cinnamates); 0 (N-(3-methoxyphenyl)-4-chlorocinnamanilide); 0 (Phalpha1beta toxin, Phoneutria nigriventer); 0 (Spider Venoms); 0 (TRPV Cation Channels); 0 (TRPV1 receptor); S07O44R1ZM (Capsaicin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170717
[Lr] Data última revisão:
170717
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE


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[PMID]:28422977
[Au] Autor:Robinson JR; Kennedy VE; Doss Y; Bastarache L; Denny J; Warner JL
[Ad] Endereço:Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States of America.
[Ti] Título:Defining the complex phenotype of severe systemic loxoscelism using a large electronic health record cohort.
[So] Source:PLoS One;12(4):e0174941, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Systemic loxoscelism is a rare illness resulting from the bite of the recluse spider and, in its most severe form, can lead to widespread hemolysis, coagulopathy, and death. We aim to describe the clinical features and outcomes of the largest known cohort of individuals with moderate to severe loxoscelism. METHODS: We performed a retrospective, cross sectional study from January 1, 1995, to December 31, 2015, at a tertiary-care academic medical center, to determine individuals with clinical records consistent with moderate to severe loxoscelism. Age-, sex-, and race-matched controls were compared. Demographics, clinical characteristics, laboratory measures, and outcomes of individuals with loxoscelism are described. Case and control groups were compared with descriptive statistics and phenome-wide association study (PheWAS). RESULTS: During the time period, 57 individuals were identified as having moderate to severe loxoscelism. Of these, only 33% had an antecedent spider bite documented. Median age of individuals diagnosed with moderate to severe loxoscelism was 14 years old (IQR 9.0-24.0 years). PheWAS confirmed associations of systemic loxoscelism with 29 other phenotypes, e.g., rash, hemolytic anemia, and sepsis. Hemoglobin level dropped an average of 3.1 g/dL over an average of 2.0 days (IQR 2.0-6.0). Lactate dehydrogenase and total bilirubin levels were on average over two times their upper limit of normal values. Eighteen individuals of 32 tested had a positive direct antiglobulin (Coombs') test. Mortality was 3.5% (2/57 individuals). CONCLUSION: Systemic loxoscelism is a rare but devastating process with only a minority of patients recalling the toxic exposure; hemolysis reaches a peak at 2 days after admission, with some cases taking more than a week before recovery. In endemic areas, suspicion for systemic loxoscelism should be high in individuals, especially children and younger adults, presenting with a cutaneous ulcer and hemolysis or coagulopathy, even in the absence of a bite exposure history.
[Mh] Termos MeSH primário: Aranha Marrom Reclusa/patogenicidade
Coagulação Intravascular Disseminada/diagnóstico
Picaduras de Aranhas/diagnóstico
Venenos de Aranha/toxicidade
[Mh] Termos MeSH secundário: Adolescente
Animais
Bilirrubina/sangue
Estudos de Casos e Controles
Criança
Estudos Transversais
Coagulação Intravascular Disseminada/sangue
Coagulação Intravascular Disseminada/mortalidade
Coagulação Intravascular Disseminada/fisiopatologia
Registros Eletrônicos de Saúde/estatística & dados numéricos
Feminino
Hemoglobinas/metabolismo
Hemólise/efeitos dos fármacos
Seres Humanos
L-Lactato Desidrogenase/sangue
Masculino
Fenótipo
Estudos Retrospectivos
Picaduras de Aranhas/sangue
Picaduras de Aranhas/mortalidade
Picaduras de Aranhas/fisiopatologia
Análise de Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hemoglobins); 0 (Spider Venoms); EC 1.1.1.27 (L-Lactate Dehydrogenase); RFM9X3LJ49 (Bilirubin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0174941


  6 / 2407 MEDLINE  
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[PMID]:28416610
[Au] Autor:Ilkan Z; Wright JR; Goodall AH; Gibbins JM; Jones CI; Mahaut-Smith MP
[Ad] Endereço:From the Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom.
[Ti] Título:Evidence for shear-mediated Ca entry through mechanosensitive cation channels in human platelets and a megakaryocytic cell line.
[So] Source:J Biol Chem;292(22):9204-9217, 2017 Jun 02.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The role of mechanosensitive (MS) Ca -permeable ion channels in platelets is unclear, despite the importance of shear stress in platelet function and life-threatening thrombus formation. We therefore sought to investigate the expression and functional relevance of MS channels in human platelets. The effect of shear stress on Ca entry in human platelets and Meg-01 megakaryocytic cells loaded with Fluo-3 was examined by confocal microscopy. Cells were attached to glass coverslips within flow chambers that allowed applications of physiological and pathological shear stress. Arterial shear (1002.6 s ) induced a sustained increase in [Ca ] in Meg-01 cells and enhanced the frequency of repetitive Ca transients by 80% in platelets. These Ca increases were abrogated by the MS channel inhibitor mechanotoxin 4 (GsMTx-4) or by chelation of extracellular Ca Thrombus formation was studied on collagen-coated surfaces using DiOC -stained platelets. In addition, [Ca ] and functional responses of washed platelet suspensions were studied with Fura-2 and light transmission aggregometry, respectively. Thrombus size was reduced 50% by GsMTx-4, independently of P2X1 receptors. In contrast, GsMTx-4 had no effect on collagen-induced aggregation or on Ca influx via TRPC6 or Orai1 channels and caused only a minor inhibition of P2X1-dependent Ca entry. The Piezo1 agonist, Yoda1, potentiated shear-dependent platelet Ca transients by 170%. Piezo1 mRNA transcripts and protein were detected with quantitative RT-PCR and Western blotting, respectively, in both platelets and Meg-01 cells. We conclude that platelets and Meg-01 cells express the MS cation channel Piezo1, which may contribute to Ca entry and thrombus formation under arterial shear.
[Mh] Termos MeSH primário: Plaquetas/metabolismo
Sinalização do Cálcio
Cálcio/metabolismo
Canais Iônicos/metabolismo
Megacariócitos/metabolismo
Trombose/metabolismo
[Mh] Termos MeSH secundário: Plaquetas/patologia
Linhagem Celular
Feminino
Seres Humanos
Canais Iônicos/antagonistas & inibidores
Masculino
Megacariócitos/patologia
Peptídeos/farmacologia
Receptores Purinérgicos P2X1/metabolismo
Venenos de Aranha/farmacologia
Estresse Mecânico
Trombose/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ion Channels); 0 (MTx4 protein, Grammostola spatulata); 0 (PIEZO1 protein, human); 0 (Peptides); 0 (Receptors, Purinergic P2X1); 0 (Spider Venoms); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170609
[Lr] Data última revisão:
170609
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.766196


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[PMID]:28400471
[Au] Autor:Tang C; Zhou X; Nguyen PT; Zhang Y; Hu Z; Zhang C; Yarov-Yarovoy V; DeCaen PG; Liang S; Liu Z
[Ad] Endereço:The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
[Ti] Título:A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel.
[So] Source:FASEB J;31(7):3167-3178, 2017 Jul.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Voltage-gated sodium channels (Na s) are activated by transiting the voltage sensor from the deactivated to the activated state. The crystal structures of several bacterial Na s have captured the voltage sensor module (VSM) in an activated state, but structure of the deactivated voltage sensor remains elusive. In this study, we sought to identify peptide toxins stabilizing the deactivated VSM of bacterial Na s. We screened fractions from several venoms and characterized a cystine knot toxin called JZTx-27 from the venom of tarantula as a high-affinity antagonist of the prokaryotic Na s Ns Ba (nonselective voltage-gated ) and NaChBac (bacterial sodium channel from ) (IC = 112 nM and 30 nM, respectively). JZTx-27 was more efficacious at weaker depolarizing voltages and significantly slowed the activation but accelerated the deactivation of Ns Ba, whereas the local anesthetic drug lidocaine was shown to antagonize Ns Ba without affecting channel gating. Mutation analysis confirmed that JZTx-27 bound to S3-4 linker of Ns Ba, with F98 being the critical residue in determining toxin affinity. All electrophysiological data and analysis suggested that JZTx-27 trapped VSM of Ns Ba in one of the deactivated states. In mammalian Na s, JZTx-27 preferably inhibited the inactivation of Na 1.5 by targeting the fourth transmembrane domain. To our knowledge, this is the first report of peptide antagonist for prokaryotic Na s. More important, we proposed that JZTx-27 stabilized the Ns Ba VSM in the deactivated state and may be used as a probe to determine the structure of the deactivated VSM of Na s.-Tang, C., Zhou, X., Nguyen, P. T., Zhang, Y., Hu, Z., Zhang, C., Yarov-Yarovoy, V., DeCaen, P. G., Liang, S., Liu, Z. A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel.
[Mh] Termos MeSH primário: Bacillus/metabolismo
Venenos de Aranha/química
Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia
Canais de Sódio Disparados por Voltagem/fisiologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sítios de Ligação
Fenômenos Eletrofisiológicos
Seres Humanos
Ligação Proteica
Conformação Proteica
Aranhas/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Spider Venoms); 0 (Voltage-Gated Sodium Channel Blockers); 0 (Voltage-Gated Sodium Channels)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170413
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201600882R


  8 / 2407 MEDLINE  
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[PMID]:28346332
[Au] Autor:Santana RC; Perez D; Dobson J; Panagides N; Raven RJ; Nouwens A; Jones A; King GF; Fry BG
[Ad] Endereço:Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia. renan.castrosantana@uq.net.au.
[Ti] Título:Venom Profiling of a Population of the Theraphosid Spider Phlogius crassipes Reveals Continuous Ontogenetic Changes from Juveniles through Adulthood.
[So] Source:Toxins (Basel);9(4), 2017 Mar 25.
[Is] ISSN:2072-6651
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Theraphosid spiders (tarantulas) are venomous arthropods found in most tropical and subtropical regions of the world. Tarantula venoms are a complex cocktail of toxins with potential use as pharmacological tools, drugs and bioinsecticides. Although numerous toxins have been isolated from tarantula venoms, little research has been carried out on the venom of Australian tarantulas. We therefore investigated the venom profile of the Australian theraphosid spider and examined whether there are ontogenetic changes in venom composition. Spiders were divided into four ontogenic groups according to cephalothorax length, then the venom composition of each group was examined using gel electrophoresis and mass spectrometry. We found that the venom of changes continuously during development and throughout adulthood. Our data highlight the need to investigate the venom of organisms over the course of their lives to uncover and understand the changing functions of venom and the full range of toxins expressed. This in turn should lead to a deeper understanding of the organism's ecology and enhance the potential for biodiscovery.
[Mh] Termos MeSH primário: Envelhecimento/metabolismo
Proteínas de Artrópodes/análise
Venenos de Aranha/análise
Aranhas/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas de Artrópodes/metabolismo
Proteômica
Venenos de Aranha/metabolismo
Aranhas/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arthropod Proteins); 0 (Spider Venoms)
[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:170328
[St] Status:MEDLINE


  9 / 2407 MEDLINE  
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[PMID]:28306751
[Au] Autor:Oldrati V; Koua D; Allard PM; Hulo N; Arrell M; Nentwig W; Lisacek F; Wolfender JL; Kuhn-Nentwig L; Stöcklin R
[Ad] Endereço:Atheris SA, Chemin d'Alcire 1, Plan-les-Ouates, Geneva, Switzerland.
[Ti] Título:Peptidomic and transcriptomic profiling of four distinct spider venoms.
[So] Source:PLoS One;12(3):e0172966, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Venom based research is exploited to find novel candidates for the development of innovative pharmacological tools, drug candidates and new ingredients for cosmetic and agrochemical industries. Moreover, venomics, as a well-established approach in systems biology, helps to elucidate the genetic mechanisms of the production of such a great molecular biodiversity. Today the advances made in the proteomics, transcriptomics and bioinformatics fields, favor venomics, allowing the in depth study of complex matrices and the elucidation even of minor compounds present in minute biological samples. The present study illustrates a rapid and efficient method developed for the elucidation of venom composition based on NextGen mRNA sequencing of venom glands and LC-MS/MS venom proteome profiling. The analysis of the comprehensive data obtained was focused on cysteine rich peptide toxins from four spider species originating from phylogenetically distant families for comparison purposes. The studied species were Heteropoda davidbowie (Sparassidae), Poecilotheria formosa (Theraphosidae), Viridasius fasciatus (Viridasiidae) and Latrodectus mactans (Theridiidae). This led to a high resolution profiling of 284 characterized cysteine rich peptides, 111 of which belong to the Inhibitor Cysteine Knot (ICK) structural motif. The analysis of H. davidbowie venom revealed a high richness in term of venom diversity: 95 peptide sequences were identified; out of these, 32 peptides presented the ICK structural motif and could be classified in six distinct families. The profiling of P. formosa venom highlighted the presence of 126 peptide sequences, with 52 ICK toxins belonging to three structural distinct families. V. fasciatus venom was shown to contain 49 peptide sequences, out of which 22 presented the ICK structural motif and were attributed to five families. The venom of L. mactans, until now studied for its large neurotoxins (Latrotoxins), revealed the presence of 14 cysteine rich peptides, out of which five were ICK toxins belonging to the CSTX superfamily. This in depth profiling of distinct ICK peptide families identified across the four spider species highlighted the high conservation of these neurotoxins among spider families.
[Mh] Termos MeSH primário: Peptídeos/metabolismo
Venenos de Aranha/metabolismo
Transcriptoma
[Mh] Termos MeSH secundário: Cromatografia Líquida
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peptides); 0 (Spider Venoms)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170318
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0172966


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[PMID]:28301520
[Au] Autor:Rahnama S; Deuis JR; Cardoso FC; Ramanujam V; Lewis RJ; Rash LD; King GF; Vetter I; Mobli M
[Ad] Endereço:Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, Australia.
[Ti] Título:The structure, dynamics and selectivity profile of a NaV1.7 potency-optimised huwentoxin-IV variant.
[So] Source:PLoS One;12(3):e0173551, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Venom-derived peptides have attracted much attention as potential lead molecules for pharmaceutical development. A well-known example is Huwentoxin-IV (HwTx-IV), a peptide toxin isolated from the venom of the Chinese bird-eating spider Haplopelma schmitdi. HwTx-IV was identified as a potent blocker of a human voltage-gated sodium channel (hNaV1.7), which is a genetically validated analgesic target. The peptide was promising as it showed high potency at NaV1.7 (IC50 ~26 nM) and selectivity over the cardiac NaV subtype (NaV1.5). Mutagenesis studies aimed at optimising the potency of the peptide resulted in the development of a triple-mutant of HwTx-IV (E1G, E4G, Y33W, m3-HwTx-IV) with significantly increased potency against hNaV1.7 (IC50 = 0.4 ± 0.1 nM) without increased potency against hNaV1.5. The activity of m3-HwTx-IV against other NaV subtypes was, however, not investigated. Similarly, the structure of the mutant peptide was not characterised, limiting the interpretation of the observed increase in potency. In this study we produced isotope-labelled recombinant m3-HwTx-IV in E. coli, which enabled us to characterise the atomic-resolution structure and dynamics of the peptide by NMR spectroscopy. The results show that the structure of the peptide is not perturbed by the mutations, whilst the relaxation studies reveal that residues in the active site of the peptide undergo conformational exchange. Additionally, the NaV subtype selectivity of the recombinant peptide was characterised, revealing potent inhibition of neuronal NaV subtypes 1.1, 1.2, 1.3, 1.6 and 1.7. In parallel to the in vitro studies, we investigated NaV1.7 target engagement of the peptide in vivo using a rodent pain model, where m3-HwTx-IV dose-dependently suppressed spontaneous pain induced by the NaV1.7 activator OD1. Thus, our results provide further insight into the structure and dynamics of this class of peptides that may prove useful in guiding the development of inhibitors with improved selectivity for analgesic NaV subtypes.
[Mh] Termos MeSH primário: Canal de Sódio Disparado por Voltagem NAV1.7/efeitos dos fármacos
Venenos de Aranha/química
Venenos de Aranha/farmacologia
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Espectroscopia de Ressonância Magnética
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Técnicas de Patch-Clamp
Conformação Proteica
Proteínas Recombinantes/efeitos dos fármacos
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NAV1.7 Voltage-Gated Sodium Channel); 0 (Recombinant Proteins); 0 (SCN9A protein, human); 0 (Spider Venoms); 0 (huwentoxin IV, Selenocosmia huwena)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173551



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