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Nous avons étudié le métabolome des globules rouges (GR) chez des patients atteints de polyarthrite rhumatoïde (PR) naïfs de traitement de fond afin d'identifier des signatures métaboliques permettant de distinguer les PR des sujets sains et les répondeurs au méthotrexate (MTX) des non-répondeurs. Les métabolites ont été extraits et identifiés dans les globules rouges et le plasma par chromatographie liquide et spectrométrie de masse. Les signatures métaboliques GR de PR naïfs de MTX et de 39 sujets sains ont été comparées. Nous avons également comparé les métabolomes des GR de 25 PR, avant (M0) et après un traitement de 3 mois par MTX (M3), entre répondeurs et non-répondeurs. Une signature métabolomique des GR a permis de distinguer les patients atteints de PR des sujets sains. La signature contenait principalement des acides aminés (AA) (comme la L-citrulline ou l'histidine, [ p < 0,05]) et incluait l'ergothionéine (EGT), qui était moins concentrée dans les GR de la PR (fold change = 0,66 ; p = 0,016). Dans la PR, la concentration d'EGT dans les GR dosée à M0 était plus faible chez les patients répondant au MTX à M3 (p = 0,036) (figures 1 et 2). La métabolomique des GR a permis de mettre en évidence d'EGT, un AA dérivé de l'alimentation et indétectable dans le plasma, comme potentiel marqueur de la PR et de la réponse au traitement par méthotrexate. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents an overview of the main actions and projects of the ANR TECSAN “CancerSensor” during the 2011–2014 period. The project aims to develop and validate a quantitative, non-invasive therapeutic tool to detect selected urinary modified nucleosides as biomarkers of colorectal cancer chemotherapy and to monitor in fine the efficiency of the chemotherapy. A methodology has been developed to generate a bulk acoustic wave molecularly imprinted polymer sensor (SAW-MIP) for the detection of various nucleosides and nucleotides of interest. A rapid and sensitive mass spectrometry method has been also developed. [Copyright &y& Elsevier]

Abstract: In higher plants and some fungi, heavy metals induce the synthesis of chelating peptides known as phytochelatins (PCs). They are characterized by the general structure (γ-Glu-Cys) n -Gly, but in some plant species, the C-terminal glycine can be replaced by serine, glutamine, glutamate or alanine, leading to iso-phytochelatins (iso-PCs). Although the distribution of iso-PCs is considered to differ from one species to another, we previously showed that Arabidopsis thaliana (A. thaliana) cells are able to synthesize most PC-related peptides (PCs and iso-PCs) described in the literature. We also observed an accumulation of the dipeptide γ-glutamylcysteine (γ-EC) when cadmium (Cd) (200 μM) was added to the culture medium, suggesting that either glutathione synthetase or glycine availability could be a limiting factor for the biosynthesis of PC-related peptides. In this context, the aim of the present work was to seek new insights into the regulation of PC synthesis by performing metabolic profiling using liquid chromatography–mass spectrometry. The levels of PC-related peptides and their precursors were measured in A. thaliana cells following Cd exposure. A range of doses (0, 50, 200 and 400 μM CdNO3) and kinetic studies (from 1 to 48 h) showed a dose threshold (50 μM CdNO3) and a lag time between the appearance of PCs and iso-PCs concomitant with the γ-EC accumulation induced by Cd, occurring at cadmium concentrations above 50 μM. This accumulation was suppressed by supplementation of the culture medium with 25 mM glycine. Glycine supplementation had a limited impact on the concentrations of glutathione and PCs whereas the levels of most iso-PCs were significantly increased. Taken together, these results indicate that GSH is involved in the biosynthesis of the iso-PCs in vivo, and that the biosynthesis of PC-related peptides is limited by the availability of glycine in the presence of high cadmium concentrations. [Copyright &y& Elsevier]

Abstract: Metabolic signatures of specialized circulating hematopoietic cells in physiological or human hematological diseases start to be described. We use a simple and highly reproductive extraction method of erythrocytes metabolites coupled with a liquid chromatography-mass spectrometry based metabolites profiling method to determine metabolomes of normal and sickle cell erythrocytes. Sickle cell erythrocytes and normal erythrocytes metabolomes display major differences in glycolysis, in glutathione, in ascorbate metabolisms and in metabolites associated to membranes turnover. In addition, the amounts of metabolites derived from urea cycle and NO metabolism that partly take place within erythrocyte were different between normal and sickle cell erythrocytes. These results show that metabolic profiling of red blood cell diseases can now be determined and might indicate new biomarkers that can be used for the follow-up of sickle cell patients. [ABSTRACT FROM AUTHOR]