Protein folding activity of ribosomal rna is a selective target of two unrelated antiprion drugs

Background: 6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases.Methodology/Principal Findings: Here we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demonstrate an RNA-dependent interaction of 6AP and GA with the ribosome. These specific interactions have no effect on the peptidyl transferase activity of the ribosome or on global translation. In contrast, 6AP and GA specifically inhibit the ribosomal RNA-mediated protein folding activity of the ribosome.Conclusion/Significance: 6AP and GA are therefore the first compounds to selectively inhibit the protein folding activity of the ribosome. They thus constitute precious tools to study the yet largely unexplored biological role of this protein folding activity

Protein Folding Activity of Ribosomal RNA Is a Selective Target of Two Unrelated Antiprion Drugs

International audienceBACKGROUND: 6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demonstrate an RNA-dependent interaction of 6AP and GA with the ribosome. These specific interactions have no effect on the peptidyl transferase activity of the ribosome or on global translation. In contrast, 6AP and GA specifically inhibit the ribosomal RNA-mediated protein folding activity of the ribosome. CONCLUSION/SIGNIFICANCE: 6AP and GA are therefore the first compounds to selectively inhibit the protein folding activity of the ribosome. They thus constitute precious tools to study the yet largely unexplored biological role of this protein folding activity

Disparités intra-départementales dans les modalités de présentation du cancer colorectal et effets de la mise en place de la campagne de dépistage généralisé (étude réalisée dans deux hôpitaux de l'AP-HP du 92 situés dans des bassins de vie à caractéristiques socio-économiques différentes)

PARIS6-Bibl. St Antoine CHU (751122104) / SudocSudocFranceF

Circonstances de découverte et modalités de prise en charge des patients atteints de cancers colorectaux à l'hôpital Louis Mourier de janvier 2002 à décembre 2004

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Efficacité de la prise en charge du sevrage alcoolique de patients hospitalisés pour pathologie organique dans un service d'hépato-gastroentérologie (étude prospective sur 3 ans)

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Étude de la sensibilité viscérale rectale chez l'homme sain

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Dysbiose et métabolisme des acides biliaires (implications au cours du syndrome de l intestin irritable)

Le syndrome de l'intestin irritable associe douleurs abdominales chroniques et troubles du transit. C'est une pathologie digestive fréquente, qui dans sa physiopathologie inclue le concept de dysbiose, i.e les perturbations du microbiote intestinal (l'ensemble des micro organismes contenus dans un intestin). La dysbiose sous entend des perturbations du dialogue hôte-microbiote conduisant à la maladie, concept essentiellement descriptif à ce jour. Les acides biliaires sont synthétisés par le foie, métabolisés par les bactéries puis réabsorbés par l'intestin - donc potentiellement acteurs de ce dialogue. D'autres axes physiopathologiques incluent motricité, perméabilité, et sécrétion intestinale, des fonctions également régulées par les acides biliaires, via le récepteur membranaire TGR5. Ce travail présente et discute, à travers deux publications scientifiques les liens entre syndrome de l'intestin irritable, dysbiose, et récepteur TGR5The irritable bowel syndrome associates chronic abdominal pain and altered bowel transit. This is a common digestive disorder, which in its pathophysiology include the concept of dysbiosis, i.e disruption of the intestinal microbiota (overall micro organisms in a gut). Dysbiosis implies alterations of the host-microbiota dialogue leading to disease, a mainly descriptive concept to date. Bile acids are synthesized by the liver and metabolized by bacteria then reabsorbed from the intestine - so potentially involved in this dialogue. Other pathophysiological axes include motor, permeability, and intestinal secretion, and theses are functions also regulated by bile acids, through the membrane receptor TGR5. This work presents and discusses, through two scientific publications, the links between irritable bowel syndrome, dysbiosis, and TGR5 receptorPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

Food consumption and dietary intakes in 36,448 adults and their association with irritable bowel syndrome: Nutrinet-Santé study

Introduction: Diet plays an important role for patients with irritable bowel syndrome (IBS). The aim of this study was to compare the diets in terms of food consumption and nutrient intake between subjects with IBS and controls in a large French population. Methods: This study included 36,448 subjects from the Nutrinet-Santé cohort study, who completed a questionnaire pertaining to functional bowel disorders based on the Rome III criteria. Dietary data were obtained from at least three self-administered 24 h records via the internet. Association between IBS and diet was evaluated by comparison tests controlled for gender, age and total energy intake (ANCOVA tests). Results: Subjects included were mainly women (76.9%) and the mean age was 50.2 ± 14.2 years. Among these individuals, 1870 (5.1%) presented with IBS. Compared to healthy controls, they had significantly lower consumption of milk (74.6 versus 88.4 g/day; p < 0.0001), yogurt (108.4 versus 115.5 g/day; p = 0.001), fruits (192.3 versus 203.8 g/day; p < 0.001), and higher soft non-sugared beverages (1167.2 versus 1122.9 ml/day; p < 0.001). They had higher total energy intake (2028.9 versus 1995.7 kcal/day; p < 0.001), with higher intakes of lipids (38.5 versus 38.1% of total energy intake; p = 0.001) and lower intakes of proteins (16.4 versus 16.8% of total energy intake; p < 0.0001), as well as micronutrients (calcium, potassium, zinc and vitamins B2, B5 and B9, all p < 0.0001). Conclusions: In this large sample, these findings suggest that dietary intake of subjects suffering from IBS differs from that of control subjects. They may have adapted their diet according to symptoms following medical or non-medical recommendations