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dc.contributor.authorFolli, Franco
dc.contributor.authorGuzzi, Valeria
dc.contributor.authorPerego, Lucia
dc.contributor.authorColetta, Dawn K.
dc.contributor.authorFinzi, Giovanna
dc.contributor.authorPlacidi, Claudia
dc.contributor.authorLa Rosa, Stefano
dc.contributor.authorCapella, Carlo
dc.contributor.authorSocci, Carlo
dc.contributor.authorLauro, Davide
dc.contributor.authorTripathy, Devjit
dc.contributor.authorJenkinson, Christopher
dc.contributor.authorParoni, Rita
dc.contributor.authorOrsenigo, Elena
dc.contributor.authorCighetti, Giuliana
dc.contributor.authorGregorini, Luisa
dc.contributor.authorStaudacher, Carlo
dc.contributor.authorSecchi, Antonio
dc.contributor.authorBachi, Angela
dc.contributor.authorBrownlee, Michael
dc.contributor.authorFiorina, Paolo
dc.date.accessioned2011-02-10T20:41:02Z
dc.date.issued2010
dc.identifier.citationFolli, Franco, Valeria Guzzi, Lucia Perego, Dawn K. Coletta, Giovanna Finzi, Claudia Placidi, Stefano La Rosa, et al. 2010. Proteomics Reveals Novel Oxidative and Glycolytic Mechanisms in Type 1 Diabetic Patients' Skin Which Are Normalized by Kidney-Pancreas Transplantation. PLoS ONE 5(3): e9923.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4724157
dc.description.abstractBackground: In type 1 diabetes (T1D) vascular complications such as accelerated atherosclerosis and diffused macro-/microangiopathy are linked to chronic hyperglycemia with a mechanism that is not yet well understood. End-stage renal disease (ESRD) worsens most diabetic complications, particularly, the risk of morbidity and mortality from cardiovascular disease is increased several fold. Methods and Findings: We evaluated protein regulation and expression in skin biopsies obtained from T1D patients with and without ESRD, to identify pathways of persistent cellular changes linked to diabetic vascular disease. We therefore examined pathways that may be normalized by restoration of normoglycemia with kidney-pancreas (KP) transplantation. Using proteomic and ultrastructural approaches, multiple alterations in the expression of proteins involved in oxidative stress (catalase, superoxide dismutase 1, Hsp27, Hsp60, ATP synthase δ chain, and flavin reductase), aerobic and anaerobic glycolysis (ACBP, pyruvate kinase muscle isozyme, and phosphoglycerate kinase 1), and intracellular signaling (stratifin-14-3-3, S100-calcyclin, cathepsin, and PPI rotamase) as well as endothelial vascular abnormalities were identified in T1D and T1D+ESRD patients. These abnormalities were reversed after KP transplant. Increased plasma levels of malondialdehyde were observed in T1D and T1D+ESRD patients, confirming increased oxidative stress which was normalized after KP transplant. Conclusions: Our data suggests persistent cellular changes of anti-oxidative machinery and of aerobic/anaerobic glycolysis are present in T1D and T1D+ESRD patients, and these abnormalities may play a key role in the pathogenesis of hyperglycemia-related vascular complications. Restoration of normoglycemia and removal of uremia with KP transplant can correct these abnormalities. Some of these identified pathways may become potential therapeutic targets for a new generation of drugs.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0009923en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848014/pdf/en_US
dash.licenseLAA
dc.subjectdiabetes and endocrinologyen_US
dc.subjectcell biologyen_US
dc.subjectcell signalingen_US
dc.subjectendocrinologyen_US
dc.subjecttype 1 diabetesen_US
dc.titleProteomics Reveals Novel Oxidative and Glycolytic Mechanisms in Type 1 Diabetic Patients' Skin Which Are Normalized by Kidney-Pancreas Transplantationen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorFiorina, Paolo
dc.date.available2011-02-10T20:41:02Z
dash.affiliation.otherHMS^Pediatrics-Children's Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0009923*
dash.authorsorderedfalse
dash.contributor.affiliatedFiorina, Paolo


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