Actualités

Marie-Lynda BOURESSAM soutiendra sa thèse de doctorat intitulée "Importance de la S-nitrosation des récepteurs cérébrovasculaires de l’angiotensine II" le mercredi 4 juillet 2018 à 13h dans la salle des Thèses (Lionnois) à Nancy.

Le jury est composé de :

- Mme Isabelle MARGAILL (Rapporteur, PR, EA4475, Université Paris Descartes, Paris)

- Mr Daniel HENRION (Rapporteur, DR, UMR CNRS 6261 - INSERM 1083, Université d’Angers, Angers)

- Mme Isabelle LARTAUD (Examinateur, PR, EA3452 CITHEFOR, Université de Lorraine, Nancy, Directeur de thèse)

- Mr François DUPUIS (Examinateur, MCU, EA3452 CITHEFOR, Université de Lorraine, Nancy, Co-directeur de thèse)

- Mr Arnaud BIANCHI (Membre invité, IR1, UMR7365, Université de Lorraine, Vandoeuvre les Nancy)

L'article "Intestinal absorption of S-nitrosothiols: permeability and transport mechanisms" vient de paraître dans le journal "Biochemical Pharmacology"

Auteurs : Justine Bonetti, Yi Zhou, Marianne Parent, Igor Clarot, Haiyan Yu, Isabelle Fries-Raeth, Pierre Leroy, Isabelle Lartaud, Caroline Gaucher

Référence de l'article : Biochem Pharmacol. 2018 Jun 21. pii: S0006-2952(18)30231-4. doi: 10.1016/j.bcp.2018.06.018.

Abstract :

S-Nitrosothiols, a class of NO donors, demonstrate potential benefits for cardiovascular diseases. Drugs for such chronic diseases require long term administration preferentially through the oral route. However, the absorption of S-nitrosothiols by the intestine, which is the first limiting barrier for their vascular bioavailability, is rarely evaluated. Using an in vitro model of intestinal barrier, based on human cells, the present work aimed at elucidating the mechanisms of intestinal transport (passive or active, paracellular or transcellular pathway) and at predicting the absorption site of three S-nitrosothiols: S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-l-cysteine (NACNO) and S-nitroso-N-acetyl-d-penicillamine (SNAP). These S-nitrosothiols include different skeletons carrying the nitroso group, which confer different physico-chemical characteristics and biological activities (antioxidant and anti-inflammatory). According to the values of apparent permeability coefficient, the three S-nitrosothiols belong to the medium class of permeability. The evaluation of the bidirectional apparent permeability demonstrated a passive diffusion of the three S-nitrosothiols. GSNO and NACNO preferentially cross the intestinal barrier though the transcellular pathway, while SNAP followed both the trans- and paracellular pathways. Finally, the permeability of NACNO was favoured at pH 6.4, which is close to the pH of the jejunal part of the intestine. Through this study, we determined the absorption mechanisms of S-nitrosothiols and postulated that they can be administrated through the oral route.

L'EA 3452 a acquis récemment deux nouveaux équipements (voir photo), grâce au soutien financier du CPER (Contrat de Plan Etat-Région) :

• un appareil de dissolution à flux continu USP 4
• une électrode à monoxyde d'azote ainsi que son système d'acquisition

Ces deux appareils sont en service et viennent compléter l'équipement des plateaux techniques "formulation" et "physico-chimie".

L'article "No answer to the lack of specificity: mouse monoclonal antibody targeting the angiotensin II type 1 receptor AT1 fails to recognize its target" vient de paraître dans le journal "Naunyn-Schmiedeberg's Archives of Pharmacology"

Auteurs : Marie-Lynda Bouressam, Isabelle Lartaud, François Dupuis, Sandra Lecat

Référence de l'article : 2018 Jun 4. doi: 10.1007/s00210-018-1522-4. [Epub ahead of print]

Abstract :

Numerous antibodies targeting G protein-coupled receptors (GPCRs) have been described as non-specific among the polyclonal antibodies against angiotensin II type 1 receptor (AT1). We have tested the newly developed AT1 receptor mouse monoclonal antibody for its specificity. Human embryonic kidney (HEK293) cells, which do not endogenously express AT1 receptor, were transfected in order to overexpress a fluorescently labeled enhanced green fluorescent protein (EGFP)-tagged human AT1 receptor. Western blot and immunofluorescence assays were performed to test the specificity of the Santa Cruz monoclonal antibody sc-57036. These results were compared to the ones obtained with the polyclonal sc-1173 anti-AT1 receptor antibodies that have already been described as non-specific. While the positive controls using GFP antibodies detected the EGFP-tagged AT1 receptor, both polyclonal and monoclonal anti-AT1 receptor antibodies failed to specifically recognize the corresponding band by Western blot, as similar bands were revealed in either transfected or non-transfected cells. It also failed to detect AT1 receptor in immunofluorescence experiments. The lack of target recognition of the monoclonal AT1 receptor antibody in our experimental conditions suggests that this antibody could give misleading results such as misidentification of the protein. To our knowledge, no specific antibodies targeting AT1 receptors have been developed so far and the field is thus in need of new technical developments.

Programme pour les conférences du vendredi 15 juin 2018

Conférence du Dr Amedea B Seabra du Center for Natural and Human Sciences Federal University of ABC (Brésil) le 15 juin à la Faculté de Pharmacie de Nancy

"Nitric oxide releasing biomaterials for biomedical and agricultural applications"

The free radical nitric oxide (NO) plays a key role in several biological processes in mammals, such as the control of vasodilation, the immunological responses, the inhibition of platelet adhesion, the cell communication, anti-cancer activities, and the wound healing. In addition, NO is recognized as important molecule in several physiologic process in plants, including break seed dormancy, stimulate plant germination and greening, control iron homeostasis in plants, and improve plant tolerance to salinity, metal toxicity, temperature and drought stress. As a free radical, NO donors are administrated in several applications. Among them, S-nitrosothiols (RSNOs) are an important class of NO donors, since they spontaneously decompose releasing NO, and this decomposition can be triggered by light irradiation (visible region). Several papers in the literature reveal that the combination of nanotechnology and RSNOs is a promising strategy to allow the therapeutic uses of NO. In this context, this presentation focuses on the synthesis strategies, characterization, in vitro and in vivo applications of NO-based metallic and polymeric nanoparticles, hydrogels and films  for biomedical and agriculture applications.

Lors de la 3ème édition du congrès “Analytical methods to study oxidative damages, antioxidants and drugs” qui se déroulera du 24 au 26 Mai 2018 à Bialystok (Pologne), le Dr Caroline GAUCHER donnera une conférence intitulée "Protein S-nitrosation as a biomarker of nitric oxide bioavailability under oxidative stress"

L'article "Glutathione: antioxidant properties dedicated to nanotechnologies" vient de paraître dans le journal "Antioxidants", special issue "Inspired by Nature: Antioxidants and Nanotechnologies".

Auteurs : Gaucher C., Boudier A., Bonetti J., Clarot I., Leroy P., Parent M.

Référence de l'article : Antioxidants 2018, 7(5), 62; https://doi.org/10.3390/antiox7050062

Abstract :

Which scientist has never heard of glutathione (GSH)? This well-known low-molecular-weight tripeptide is perhaps the most famous natural antioxidant. However, the interest in GSH should not be restricted to its redox properties. This multidisciplinary review aims to bring out some lesser-known aspects of GSH, for example, as an emerging tool in nanotechnologies to achieve targeted drug delivery. After recalling the biochemistry of GSH, including its metabolism pathways and redox properties, its involvement in cellular redox homeostasis and signaling is described. Analytical methods for the dosage and localization of GSH or glutathiolated proteins are also covered. Finally, the various therapeutic strategies to replenish GSH stocks are discussed, in parallel with its use as an addressing molecule in drug delivery.

Communication orale au congrès Printemps de la Cardiologie :

S-nitrosation decreases AT1 receptor mediated vasoconstriction and myogenic tone on rat middle cerebral arteries par M-L BOURESSAM, Doctorante