Obiettivo Endoplasmic reticulum (ER) oxidation 1 (ERO1) trasfers disulfide bonds to protein disulfide isomerase (PDI) and is essential for oxidative protein folding in simple eukaryotes such as yeast and worms. Higher eucaryotes have alternative pathways for disulfide bond formation (Zito et al., 2010). Recently we have discovered that the ER localized peroxiredoxin 4 (PRDX4) is able to couple use of hydroperoxides for oxidative protein folding, independently of ERO1 (Zito et al., 2010b). Hydrogen peroxide production is coupled both to nutrient assimilation and to insulin signaling whereas disulfide bond formation is limiting to the production of important signaling molecules such as insulin itself (in nutrient and insulin-responsive beta cells) and adipokines (in insulin responsive adipose tissue). The aim of this proposal is to evaluate, in cultured cells and intact mice, the impact of PRDX4 and ERO1 activity on the biosynthesis and the functional state of insulin and adypokines and consequently on intermediary metabolism. Recent evidence indicates that disulfide bond formation can be manipulated with chemical probes (Blais et al., 2010). Therefore the proposed study may bring to light novel targets for pharmacological intervention in diabetes and insulin resistance states. Campo scientifico natural scienceschemical scienceselectrochemistryelectrolysismedical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein folding Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Invito a presentare proposte FP7-PEOPLE-2010-RG Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IRG - International Re-integration Grants (IRG) Coordinatore THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Contributo UE € 100 000,00 Indirizzo TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Regno Unito Mostra sulla mappa Regione East of England East Anglia Cambridgeshire CC Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Renata Schaeffer (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
