Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
ISSN: 0933-7407

hal-01632369
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01632369

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : Ants have evolved venoms rich in peptides and proteins used for predation, defense, and communication. However, they remain extremely understudied due to the minimal amount of venom secreted by each ant. The present study investigated the differences in the proteome and peptidome of the venom from the bullet ant, Paraponera clavata. Venom samples were collected from a single colony either by manual venom gland dissection or by electrical stimulation and were compared using proteomic methods. Venom proteins were separated by 2D-PAGE and identified by nanoLC-ESI-QTOF MS/MS. Venom peptides were initially separated using C18 reversed-phase high-performance liquid chromatography, then analyzed by MALDI-TOF MS. The proteomic analysis revealed numerous proteins that could be assigned a biological function (total 94), mainly as toxins, or roles in cell regulation and transport. This investigation found that ca. 73% of the proteins were common to venoms collected by the two methods. The peptidomic analysis revealed a large number of peptides (total 309) but with <20% shared by the two collection methods. There was also a marked difference between venoms obtained by venom gland dissection from different ant colonies. These findings demonstrate the rich composition and variability of P. clavata venom.
ISSN: 1535-3893

hal-01603415
https://hal.archives-ouvertes.fr/hal-01603415
DOI : 10.1021/acs.jproteome.6b00948
PRODINRA : 406775
PUBMED : 28118015

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection and inflammatory diseases). Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage Kinase domain-Like) associated in a multi-protein complex called necrosome. In order to find new inhibitors for use in human therapy, a chemical library containing highly diverse chemical structures was screened using a cell-based assay. The compound 6E11, a natural product derivative, was characterized as a positive hit. Interestingly, this flavanone compound: inhibits necroptosis induced by death receptors ligands TNF-α (Tumor Necrosis Factor) or TRAIL (TNF-Related Apoptosis-Inducing Ligand); is an extremely selective inhibitor, among kinases, of human RIPK1 enzymatic activity with a nM Kd; has a non-ATP competitive mode of action and a novel putative binding site; is weakly cytotoxic towards human primary blood leukocytes or retinal pigment epithelial cells at effective concentrations; protects human aortic endothelial cells (HAEC) from cold hypoxia/reoxygenation injury more effectively than necrostatin-1 (Nec-1) and Nec-1s. Altogether, these data demonstrate that 6E11 is a novel potent small molecular inhibitor of RIPK1-driven necroptosis.
ISSN: 2045-2322

hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/file/s41598-017-12788-4.pdf
DOI : 10.1038/s41598-017-12788-4

Éditeur(s) : HAL CCSD
Résumé : International audience
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis. By using competition binding assay and recombinant kinase assays, we demonstrated that Sib is a rather specific competitive RIPK1 inhibitor. Molecular docking analysis shows that Sib is trapped closed to human RIPK1 adenosine triphosphate-binding site in a relatively hydrophobic pocket locking RIPK1 in an inactive conformation. In agreement with its RIPK1 inhibitory property, Sib inhibits both TNF-induced RIPK1-dependent necroptosis and RIPK1-dependent apoptosis. Finally, Sib protects mice from concanavalin A-induced hepatitis. These results reveal the small-molecule Sib as a new RIPK1 inhibitor potentially of interest for the treatment of immune-dependent hepatitis. © 2017 Federation of European Biochemical Societies
ISSN: 1742464X

hal-01616420
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616420
DOI : 10.1111/febs.14176
PUBMED : 28715128

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Introduction L’objectif de cette étude est de disposer de données qualitatives et quantitatives sur la contamination de l’environnement intérieur hospitalier, microbiologique et chimique, afin d’évaluer l’exposition du personnel, des visiteurs et des patients et la variabilité spatio-temporelle de la contamination. Méthodes L’étude s’est déroulée dans différents lieux des CHU de Rennes et de Nancy : hall d’accueil, salle de soins infirmiers, salle de réveil post-opératoire, chambre d’un patient, unité de désinfection des endoscopes, laboratoire de parasitologie et salle de découpe de plâtres. Deux campagnes de prélèvement ont eu lieu en été 2014 et en hiver 2015. Les méthodes de prélèvement étaient nombreuses et complémentaires (Fig. 1). L’analyse des données a été réalisée sous IBM SPSS grâce au test de Mann-Whitney et le coefficient de corrélation de Pearson. Résultats Les concentrations d’aldéhydes, de composés organiques volatils (COV) et semi-volatils étaient faibles à très faibles dans les 2 établissements. Étaient détectables, mais sans différences globales entre les 2 établissements : la contamination fongique (m = 226 UFC/m3 ; p = 0,97) ou bactérienne (m = 352 UFC/m3 ; p = 0,14), les particules PM2,5 (m = 2,1 μg/m3 ; p = 0,97) et PM10 (m = 6,6 μg/m3 ; p = 0,84). Sur le plan saisonnier, la contamination fongique était plus importante en été pour les 2 établissements (p = 0,002). La contamination bactérienne ne varie pas significativement entre les locaux (p = 0,14) contrairement à la contamination fongique (p = 0,02) et particulaires PM2,5 (p = 0,01) ou PM10 (p = 0,01). Cette dernière est plus importante dans le hall (m = 879 UFC/m3), le laboratoire de parasitologie (m = 333 UFC/m3) et la salle de plâtre (m = 310 UFC/m3). Nous ne retrouvons pas de corrélation significative entre le nombre de personnes, le taux de CO2, l’humidité relative et le dénombrement bactérien ou fongique. Néanmoins nous retrouvons une relation forte entre la température du local et la contamination bactérienne (r = 0,7, p = 0,008) ou la contamination fongique (r = 0,56, p = 0,045) d’une part, et entre la contamination fongique et les PM10 (r = 0,52, p = 0,022) d’autre part. Conclusion Notre étude montre une très faible contamination par les aldéhydes, COV et sCOV comparativement à d’autres lieux publics. La forte variabilité spatio-temporelle de la contamination fongique et particulaire est liée à la saison, à l’activité et à la ventilation
ISSN: 1156-5233

hal-01334070
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334070
DOI : 10.1016/j.mycmed.2016.04.026

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
ISSN: 0933-7407

hal-01659242
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01659242
DOI : 10.1111/myc.12674