Dipartimento di Scienze Chimiche, Universita di Catania, Viale Andrea Doria 6, 95125 Catania, Italy. grassog@unict.it
Consorzio Interuniversitario di Ricerca in Chimica Dei Metalli Nei Sistemi Biologici, Via C. Ulpiani 27, I-70126 Bari, Italy
Istituto Biostrutture e Bioimmagini, CNR, Viale A. Doria 6, 95125 Catania, Italy
Consorzio I.N.B.B., Viale Delle Medaglie d'Oro 305, 00136, Roma, Italy
University of Catanzaro, Campus Universitario, Viale Europa, 88100 Catanzaro, Italy
NEST- Center for Nanotechnology Innovation, Piazza San Silvestro, 12, Pisa, Italy
References: Not available.
Metal ions affect insulin-degrading enzyme activity
Insulin degradation is a finely tuned process that plays a major role in controlling insulin action and most evidence supports IDE (insulin-degrading enzyme) as the primary degradative agent. However, the biomolecular mechanisms involved in the interaction between IDE and its substrates are often obscure, rendering the specific enzyme activity quite difficult to target. On the other hand, biometals, such as copper, aluminum and zinc, have an important role in pathological conditions such as Alzheimer's disease or diabetes mellitus. The metabolic disorders connected with the latter lead to some metallostasis alterations in the human body and many studies point at a high level of interdependence between diabetes and several cations. We have previously reported (Grasso et al., Chem. Eur. J. 17 (2011) 2752-2762) that IDE activity toward Abeta peptides can be modulated by metal ions. Here, we have investigated the effects of different metal ions on the IDE proteolytic activity toward insulin as well as a designed peptide comprising a portion of the insulin B chain (B20-30), which has a very low affinity for metal ions. The results obtained by different experimental techniques clearly show that IDE is irreversibly inhibited by copper(I) but is still able to process its substrates when it is bound to copper(II). Copyright 2012 Elsevier Inc. All rights reserved.
Metal ions affect insulin-degrading enzyme activity
Kállay C, Dávid A, Timári S, Nagy EM, Sanna D, Garribba E, Micera G, De Bona P, Pappalardo G, Rizzarelli E, Sóvágó I * Copper(II) complexes of rat amylin fragments(554 views) Dalton T (ISSN: 1477-9234, 1477-9226, 1477-9234electronic), 2011 Oct 14; 40(38): 9711-9721. Impact Factor:3.838 ViewExport to BibTeXExport to EndNote
Bruni AC, Bernardi L, Colao R, Rubino E, Smirne N, Frangipane F, Terni B, Curcio SA, Mirabelli M, Clodomiro A, Di Lorenzo R, Maletta R, Anfossi M, Gallo M, Geracitano S, Tomaino C, Muraca MG, Leotta A, Lio SG, Pinessi L, Rainero I, Sorbi S, Nee L, Milan G, Pappata S, Postiglione A, Abbamondi N, Forloni G, St George Hyslop P, Rogaeva E, Bugiani O, Giaccone G, Foncin JF, Spillantini MG, Puccio G * Worldwide distribution of PSEN1 Met146Leu mutation: A large variability for a founder mutation(1596 views) Neurology (ISSN: 0028-3878, 1526-632x, 1526-632xelectronic), 2010 Mar 9; 74(10): 798-806. Impact Factor:8.017 ViewExport to BibTeXExport to EndNote