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Spontaneous protein deamidation of labile Asn residues, generatingl-iso-aspartates andd-aspartates, is associated with cell aging and is enhanced by an oxidative microenvironment; to minimize the damage, the isoaspar-tate residues can be ‘repaired’ by a specific l-isoaspartate (d-aspartate) protein O-methyltransferase (PIMT). | ỊFEBS Journal Accumulation of altered aspartyl residues in erythrocyte proteins from patients with Down s syndrome Patrizia Galletti1 Maria Luigia De Bonis1 Alvara Sorrentino1 Marianna Raimo1 Stefania D Angelo1 2 Iris Scala3 Generoso Andria3 Antimo D Aniello4 Diego Ingrosso1 and Vincenzo Zappia1 1 Department of Biochemistry and Biophysics Schoolof Medicine Second University of Naples Italy 2 Faculty of Motor Sciences Parthenope University Naples Italy 3 Department of Paediatrics University of Naples Federico II Italy 4 Department of Biochemistry and Molecular Biology Stazione Zoologica Anton Dohrn Villa Comunale Naples Italy Keywords Down s syndrome L-isoaspartate L-isoaspartate-O-methyltransferase oxidative stress protein deamidation Correspondence V. Zappia Dipartimento di Biochimica e Biofisica F. Cedrangolo Seconda Universita degli Studi di Napoli Via Costantinopoli 16 80138 Napoli Italy Fax 39 0815667608 Tel 39 0815667608 9 E-mail vincenzo.zappia@unina2.it Website http www.unina2.it Received 4 July 2007 revised 13 August 2007 accepted 16 August 2007 doi 10.1111 j.1742-4658.2007.06048.x Spontaneous protein deamidation of labile Asn residues generating L-iso-aspartates and D-aspartates is associated with cell aging and is enhanced by an oxidative microenvironment to minimize the damage the isoaspartate residues can be repaired by a specific L-isoaspartate D-aspartate protein ơ-methyltransferase PIMT . As both premature aging and chronic oxidative stress are typical features of Down s syndrome DS we tested the hypothesis that deamidated proteins may build up in trisomic patients. Blood samples were obtained from children with karyotypically confirmed full trisomy 21 and from age-matched healthy controls. Using recombinant PIMT as a probe we demonstrated a dramatic rise of L-iso-aspartates in erythrocyte membrane proteins from DS patients. The content of D-aspartate was also significantly increased. The integrity of the repair system was checked by evaluating .
