Traduire, mon coiffeur et moi

Illustration : Marlène Junius. Mon premier abonnement à Traduire remonte à l’hiver 2006. Un geste solidaire, qui visait à grossir le nombre des abonnés à LA revue de la SFT et, par extension, apporter du baume au cœur « aux copains » bénévoles affairés chaque trimestre à nourrir les voraces appétits de leurs lecteurs. Auparavant, mon aventure avec le trimestriel n’avait jamais franchi le cap de l’effet coupe-faim. Le survol de ses énoncés scientifiques présageait d’innombrables va-et-vient d..

Effect of prolonged treatment with tyramine on glucose tolerance in streptozotocin-induced diabetic rats

The biogenic amine tyramine has been reported to stimulatein vitro glucose transport in adipocytes, cardiomyocytes and skeletal muscle, and to improvein vivo glucose utilization in rats. These effects were dependent on amine oxidation, since they were blocked by inhibitors of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO). We thus tested in this work whether a prolonged treatment with tyramine could improve glucose tolerance in streptozotocin-induced diabetic rats. First, tyramine content of standard rodent chow was determined by HPLC and daily tyramine intake of control rats was estimated to be around 26 μmol/kg body weight. Then, tyramine was administred during 3 weeks in streptozotocin-induced diabetic rats at 29 μmol/kg by daily i.p. injection alone or together with vanadate 0.02 μmol/kg. In another group of diabetic rats, tyramine was subcutaneously delivered at 116 μmol/kg/day by osmotic minipumps. All tyramine treatments resulted in a decrease of the hyperglycemic responses to an i.p. glucose load. Adipocytes isolated from either untreated or treated diabetic rats were sensitive to the stimulation of glucose uptake by tyramine. However, diabetic animals receiving tyramine for three weeks did not recover from their hyperglycemia, hypoinsulinemia and glucosuria. These results show that the improvement of glucose tolerance induced by prolonged tyramine administration occurs in an insulin-depleted model and probably results from peripheral insulin-like actions of the oxidation of MAO/SSAO substrates, such as the stimulation of glucose uptake into adipocytes

Exosomes as intercellular signalosomes and pharmacological effectors.

International audienceCell secretion is a general process involved in various biological responses. Exosomes are part of this process and have gained considerable scientific interest in the past five years. Several steps through investigations across the last 20 years can explain this interest. First characterized during reticulocyte maturation, they were next evidenced as a key player in the immune response and cancer immunotherapy. More recently they were reported as vectors of mRNAs, miRNAs and also lipid mediators able to act on target cells. They are the only type of vesicles released from an intracellular compartment from cells in viable conditions. They appear as a vectorized signaling system operating from inside a donor cell towards either the periphery, the cytosol, or possibly to the nucleus of target cells. Exosomes from normal cells trigger positive effects, whereas those from pathological ones, such as tumor cells or infected ones may trigger non-positive health effects. Therefore regulating the biogenesis and secretion of exosomes appear as a pharmacological challenge to intervene in various pathophysiologies. Exosome biogenesis and molecular content, interaction with target cells, utilisation as biomarkers, and functional effects in various pathophysiologies are considered in this review

Anticorps anti-pentraxine au cours des maladies auto-immunes

International audienceLes pentraxines (PTXs) sont des récepteurs solubles innés classés dans les « pattern recognition receptors » (PRRs). Elles sont composées de deux sous-familles définies sur une base structurelle : les PTXs courtes et les PTXs longues. Les PTXs courtes sont représentées par la protéine C réactive (CRP) et le composant P amyloïde (SAP). La famille des PTXs longues est représentée principalement par la PTX3. Les PTXs sont impliquées dans de nombreux processus biologiques. En plus de leur fonction d'opsonine antimicrobienne, les PTXs sont aussi impliquées dans la clairance des débris cellulaires et des cellules mortes (efferocytose). Une rupture de tolérance vis-à-vis des PTXs a été mise en évidence au cours de différentes maladies auto-immunes, notamment le lupus systémique et les vascularites à ANCA. Dans cette revue de la littérature sont présentées, dans une première partie, les principales caractéristiques et fonctions biologiques des molécules de la famille des PTXs. La seconde partie comporte une synthèse des connaissances concernant les auto-anticorps dirigés contre les PTXs et leur relation avec les aspects cliniques des principales maladies auto-immunes au cours desquelles ils ont été identifiés. Les Ac anti-PTX3 font l'objet d'une présentation approfondie

Immune Cells Release MicroRNA-155 Enriched Extracellular Vesicles That Promote HIV-1 Infection

The hallmark of HIV-1 infection is the rapid dysregulation of immune functions. Recent investigations for biomarkers of such dysregulation in people living with HIV (PLWH) reveal a strong correlation between viral rebound and immune activation with an increased abundance of extracellular vesicles (EVs) enriched with microRNA-155. We propose that the activation of peripheral blood mononuclear cells (PBMCs) leads to an increased miR-155 expression and production of miR-155-rich extracellular vesicles (miR-155-rich EVs), which can exacerbate HIV-1 infection by promoting viral replication. PBMCs were incubated with either HIV-1 (NL4.3Balenv), a TLR-7/8 agonist, or TNF. EVs were harvested from the cell culture supernatant by differential centrifugation, and RT-qPCR quantified miR-155 in cells and derived EVs. The effect of miR-155-rich EVs on replication of HIV-1 in incubated PBMCs was then measured by viral RNA and DNA quantification. HIV-1, TLR7/8 agonist, and TNF each induced the release of miR-155-rich EVs by PBMCs. These miR-155-rich EVs increased viral replication in PBMCs infected in vitro. Infection with HIV-1 and inflammation promote the production of miR-155-rich EVs, enhancing viral replication. Such autocrine loops, therefore, could influence the course of HIV-1 infection by promoting viral replication

Velocity Gradient Separation Reveals a New Extracellular Vesicle Population Enriched in miR-155 and Mitochondrial DNA

Extracellular vesicles (EVs) and their contents (proteins, lipids, messenger RNA, microRNA, and DNA) are viewed as intercellular signals, cell-transforming agents, and shelters for viruses that allow both diagnostic and therapeutic interventions. EVs circulating in the blood of individuals infected with human immunodeficiency virus (HIV-1) may provide insights into pathogenesis, inflammation, and disease progression. However, distinguishing plasma membrane EVs from exosomes, exomeres, apoptotic bodies, virions, and contaminating proteins remains challenging. We aimed at comparing sucrose and iodixanol density and velocity gradients along with commercial kits as a means of separating EVs from HIV particles and contaminating protein like calprotectin; and thereby evaluating the suitability of current plasma EVs analysis techniques for identifying new biomarkers of HIV-1 immune activation. Multiple analysis have been performed on HIV-1 infected cell lines, plasma from HIV-1 patients, or plasma from HIV-negative individuals spiked with HIV-1. Commercial kits, the differential centrifugation and density or velocity gradients to precipitate and separate HIV, EVs, and proteins such as calprotectin, have been used. EVs, virions, and contaminating proteins were characterized using Western blot, ELISA, RT-PCR, hydrodynamic size measurement, and enzymatic assay. Conversely to iodixanol density or velocity gradient, protein and virions co-sedimented in the same fractions of the sucrose density gradient than AChE-positive EVs. Iodixanol velocity gradient provided the optimal separation of EVs from viruses and free proteins in culture supernatants and plasma samples from a person living with HIV (PLWH) or a control and revealed a new population of large EVs enriched in microRNA miR-155 and mitochondrial DNA. Although EVs and their contents provide helpful information about several key events in HIV-1 pathogenesis, their purification and extensive characterization by velocity gradient must be investigated thoroughly before further use as biomarkers. By revealing a new population of EVs enriched in miR-155 and mitochondrial DNA, this study paves a way to increase our understanding of HIV-1 pathogenesis