Phytoextraction process optimization : characterization of the soil bacteria flora associated to the hyperaccumulator Arabidopsis halleri

International audiencePhytotechnologies are microbial-assisted techniques that use living plants for the treatment of contaminated sites. Among these, phytoextraction based on hyperaccumulator plants such as Arabidopsis halleri, may be an option to remove trace elements in soil. One method to optimize Arabidopsis halleri's phytoextraction is the inoculation of plant roots by plant growth promoting bacteria (PGPB). In this study, we analyzed the total bacterial diversity in a Zn and Cd contaminated industrial soil (Auby, France) with restriction fragment length polymorphism (RFLP). Preliminary results showed a large bacterial diversity in Auby's soil. Cultivable bacteria were isolated and characterized for their PGPB traits (ACC deaminase activity, siderophores and Indol-Acetic-Acid (IAA) productions). Bacteria that will answer positively to the three PGPB tests will be preferentially selected, and inoculated to Arabidopsis halleri roots. Bacteria effects on plant biomass and/or accumulating yield will be presented

Optimisation de la phytoextraction : caractérisation et sélection de bactéries PGPB associées à une plante hyperaccumulatrice de Zn et Cd : Arabidopsis halleri

National audiencePhytotechnologies are microbial-assisted techniques that use living plants for the treatment of contaminated sites. Among these, phytoextraction based on hyperaccumulator plants such as Arabidopsis halleri, may be an option to remove trace elements in soil. One method to optimize Arabidopsis halleri phytoextraction is the inoculation of plant roots by plant growth promoting bacteria (PGPB). In this study, we proposed a protocol for sampling bacteria in three different soil fractions neared root system of Arabidopsis halleri: global, rhizospheric and rhizoplan. The cultivable bacteria were isolated for a Zn and Cd contaminated industrial soil (Auby, France) and were isolated and characterized for their PGPB traits : 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, siderophores and Indol-Acetic-Acid (IAA) productions). Bacteria answering positively to the three PGPB tests have been preferentially selected to be inoculated to Arabidopsis halleri root system. Bacteria effects on plant biomass and/or accumulating yield will be presented.Les phytotechnologies consistent en l'utilisation de plantes qui, par leur association avec la microflore du sol, ont la capacité de dépolluer les sites contaminés (eau, sol, sédiments). Parmi ces technologies, la phytoextraction, basée sur l'utilisation de plantes hyperaccumulatrices telle qu'Arabidopsis halleri, semble être une option pour décontaminer les sols pollués en éléments traces métalliques. Une des voies d'amélioration de la phytoextraction d'A. halleri serait l'inoculation du système racinaire de la plante par des bactéries capables de stimuler la croissance végétale (PGPB pour Plant Growth Promoting Bacteria). Dans cette étude, nous proposons un protocole d'échantillonnage des différentes fractions de sol autour de la racine : sols global, rhizosphérique et rhizoplan. Les bactéries cultivables, collectées sur un sol industriel contaminé en Zn et Cd (Auby, France), ont été isolées et analysées pour leurs caractéristiques PGPB : activité 1-aminocyclopropane-1-carboxylate (ACC) désaminase, productions de sidérophores et d'acide indole acétique (IAA). Les bactéries qui présentent trois caractères PGPB ont été préférentiellement sélectionnées pour être inoculées au niveau du système racinaire d'Arabidopsis halleri. Les effets de ces bactéries sur les paramètres de croissance de la plante et sa biomasse ou sur le rendement d'accumulation des éléments traces métalliques seront présentés

TRIM17 and TRIM28 antagonistically regulate the ubiquitination and anti-apoptotic activity of BCL2A1

International audienceBCL2A1 is an anti-apoptotic member of the BCL-2 family that contributes to chemoresistance in a subset of tumors. BCL2A1 has a short half-life due to its constitutive processing by the ubiquitin-proteasome system. This constitutes a major tumor-suppressor mechanism regulating BCL2A1 function. However, the enzymes involved in the regulation of BCL2A1 protein stability are currently unknown. Here, we provide the first insight into the regulation of BCL2A1 ubiquitination. We present evidence that TRIM28 is an E3 ubiquitin-ligase for BCL2A1. Indeed, endogenous TRIM28 and BCL2A1 bind to each other at the mitochondria and TRIM28 knock-down decreases BCL2A1 ubiquitination. We also show that TRIM17 stabilizes BCL2A1 by blocking TRIM28 from binding and ubiquitinating BCL2A1, and that GSK3 is involved in the phosphorylation-mediated inhibition of BCL2A1 degradation. BCL2A1 and its close relative MCL1 are thus regulated by common factors but with opposite outcome. Finally, overexpression of TRIM28 or knock-out of TRIM17 reduced BCLA1 protein levels and restored sensitivity of melanoma cells to BRAF-targeted therapy. Therefore, our data describe a molecular rheostat in which two proteins of the TRIM family antagonistically regulate BCL2A1 stability and modulate cell death

Utility of Cardiac Magnetic Resonance to assess association between admission hyperglycemia and myocardial damage in patients with reperfused ST-Segment Elevation Myocardial Infarction

International audienceAbstract: Aims: to investigate the association between admission hyperglycemia and myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) using Cardiac Magnetic Resonance (CMR). Methods: We analyzed 113 patients with STEMI treated with successful primary percutaneous coronary intervention. Admission hyperglycemia was defined as a glucose level >= 7.8 mmol/l. Contrast-enhanced CMR was performed between 3 and 7 days after reperfusion to evaluate left ventricular function and perfusion data after injection of gadolinium-DTPA. First-pass images (FP), providing assessment of microvascular obstruction and Late Gadolinium Enhanced images (DE), reflecting the extent of infarction, were investigated and the extent of transmural tissue damage was determined by visual scores. Results: Patients with a supramedian FP and DE scores more frequently had left anterior descending culprit artery (p = 0.02 and < 0.001), multivessel disease (p = 0.02 for both) and hyperglycemia (p < 0.001). Moreover, they were characterized by higher levels of HbA(1c) (p = 0.01 and 0.04), peak plasma Creatine Kinase (p < 0.001), left ventricular end-systolic volume (p = 0.005 and < 0.001), and lower left ventricular ejection fraction (p = 0.001 and < 0.001). In a multivariate model, admission hyperglycemia remains independently associated with increased FP and DE scores. Conclusion: Our results show the existence of a strong relationship between glucose metabolism impairment and myocardial damage in patients with STEMI. Further studies are needed to show if aggressive glucose control improves myocardial perfusion, which could be assessed using CMR

La protéine kinase ck2 (corrélation de la surexpression de la sous-unité catalytique a en immuno-histochimie à des facteurs de mauvais pronostic sur une série de 111 adénocarcinomes de prostate)

La protéine CK2 est une sérine-thréonine kinase ubiquitaire et conservée au cours de l'évolution. Elle est composée d'un dimère de 2 sous-unités régulatrices b sur lequel s'associent 2 sous-unités catalytiques a. Dans ce travail, l'expression de la CK2a a été étudiée rétrospectivement par immuno-histochimie (IHC) sur cent onze adénocarcinomes de prostate (72 du CU de Grenoble et 39 sur une puce à tissus du commerce). Les patients ont été répartis dans 3 groupes : 0/1+ (expression faible), 2+ (expression modérée) et 3+ et plus (surexpression). La CK2a est plus exprimée dans les glandes prostatiques tumorales que dans les glandes normales et son expression est majoritairement cytoplasmique (p<0.001). Le groupe surexpression (3+) regroupe 43.3% des cancers et les facteurs pronostiques y sont péjoratifs : 85% des tumeurs 3+ ont un score de Gleason supérieur ou égal à 7, 48% correspondent à des stades pT3-T4 et 63,6% présentent des emboles péri-nerveux et/ou lymphatiques. Les tumeurs des groupes 0/1+ et 2+ rassemblés ont 55.5% de score de Gleason supérieur ou égal à 7, 16% sont des pT3-T4 et 38% comportent des emboles. Ces différences sont statistiquement significatives (p<0.001 à 0.05). Il n'y a pas de données de survie disponibles pour étudier l'impact du statut CK2a sur le devenir des patients. Des études complémentaires sont nécessaires.CK2 is an ubiquitinous and highly conserved serine/threonine protein kinase. Potential substrates are >300. Its role in human cancerogenesis remains unclear, but data showed that it promotes proliferation and protect cancer cells against apoptosis. Cristallography depict an heterotetramere, with 2 regulatory subunits (CK2b) associated with 2 catalytic subunits (CK2a). In this study, we performed immunochemistry with a specific anti-CK2a polyclonal antibody. Analysis of 111 samples of human prostate adenocarcinoma showed an overexpression in 43.3% of cases. Patients in this subgroup ( overexpression group ) have bad prognostic factors: 85% with Gleason score up to 6, 48% are pT3-T4 tumors and 63.6% show perineural invasion. By comparison, these percentages are respectively 55.5%, 16% and 38% in the remaining group. Differences are statistically significant (p<0.001 to 0.05). Then, overexpression group seems to be clinically relevant, but survival data are lacking. Furthers investigations are needed to explore the exact role of CK2a in prostate cancer, and to establish if this protein represent a new biomarker.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Protein kinase CK2 in health and disease: Cellular functions of protein kinase CK2: a dynamic affair.

International audienceProtein kinase CK2 targets a vast array of substrates located in a number of cellular compartments, making the challenge of discriminating among these substrates a daunting task. However, as a signaling protein, CK2 could be targeted to different cellular compartments in response to various stress stimuli such as heat shock, UV irradiation, hypoxia, DNA damage and viral infections. This review will be focused on the evidence that the dynamic association of CK2 subunits and the substrate-dependent subcellular targeting of the enzyme are a likely point of regulation in response to a variety of signaling events. We propose that in addition to enzymatic substrate recognition, regulated CK2 localization to specific compartments should help to provide the exquisite specificity required for robust signal transduction

La protéine kinase CK2, une enzyme qui cultive la différence

La perte des mécanismes de contrôle de la progression du cycle de division cellulaire ou du déclenchement des processus d’apoptose permet aux cellules d’acquérir des propriétés décisives pour leur transformation tumorale. Plusieurs protéine kinases participent à la transduction de signaux qui neutralisent des composants de la machinerie apoptotique. Dans ce contexte, la protéine kinase CK2 (caséine kinase 2), dont la structure vient d’être élucidée, apparaît comme un régulateur déterminant pour la viabilité cellulaire. Il est concevable que la surexpression de la CK2 observée dans les cancers puisse conduire à la formation de signaux de survie contribuant à la tumorigenèse.Protein kinase CK2 (formerly known as casein kinase 2) was among the first protein kinases to be identified and characterized. Surprisingly, in spite of intense efforts, the regulation and cellular functions of CK2 remain obscure. However, recent data on its molecular structure, its signal-mediated intracellular dynamic localization and its unexpected function in cell survival have raised new interest in this enzyme. These studies reveal unique features of CK2 and highlight its importance in the transduction of survival signals

La protéine kinase ck2 (corrélation de la surexpression de la sous-unité catalytique a en immuno-histochimie à des facteurs de mauvais pronostic sur une série de 111 adénocarcinomes de prostate)

La protéine CK2 est une sérine-thréonine kinase ubiquitaire et conservée au cours de l'évolution. Elle est composée d'un dimère de 2 sous-unités régulatrices b sur lequel s'associent 2 sous-unités catalytiques a. Dans ce travail, l'expression de la CK2a a été étudiée rétrospectivement par immuno-histochimie (IHC) sur cent onze adénocarcinomes de prostate (72 du CU de Grenoble et 39 sur une puce à tissus du commerce). Les patients ont été répartis dans 3 groupes : 0/1+ (expression faible), 2+ (expression modérée) et 3+ et plus (surexpression). La CK2a est plus exprimée dans les glandes prostatiques tumorales que dans les glandes normales et son expression est majoritairement cytoplasmique (p300. Its role in human cancerogenesis remains unclear, but data showed that it promotes proliferation and protect cancer cells against apoptosis. Cristallography depict an heterotetramere, with 2 regulatory subunits (CK2b) associated with 2 catalytic subunits (CK2a). In this study, we performed immunochemistry with a specific anti-CK2a polyclonal antibody. Analysis of 111 samples of human prostate adenocarcinoma showed an overexpression in 43.3% of cases. Patients in this subgroup ( overexpression group ) have bad prognostic factors: 85% with Gleason score up to 6, 48% are pT3-T4 tumors and 63.6% show perineural invasion. By comparison, these percentages are respectively 55.5%, 16% and 38% in the remaining group. Differences are statistically significant (p<0.001 to 0.05). Then, overexpression group seems to be clinically relevant, but survival data are lacking. Furthers investigations are needed to explore the exact role of CK2a in prostate cancer, and to establish if this protein represent a new biomarker.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

New protein kinase CK2 inhibitors: jumping out of the catalytic box.

International audienceProtein kinases are central components of signal transduction cascades often dysregulated in cancer, and they represent some of the most promising drug targets. However, the target selectivity is a major concern because most described kinase inhibitors target the highly conserved ATP-binding pocket. Recently, new classes of inhibitors that do not compete with ATP and exhibit different mechanisms of action have been described. Overexpression of protein kinase CK2 is an unfavorable prognostic marker in several cancers. Consequently, CK2 has emerged as a relevant therapeutic target. Several classes of ATP-competitive inhibitors have been identified, showing variable effectiveness. The molecular architecture of this multisubunit enzyme could offer alternative strategies to inhibit CK2 functions, and this review illustrates these emerging possibilities