Proteomics reveals novel oxidative and glycolytic mechanisms in type 1 diabetic patients' skin which are normalized by kidney-pancreas transplantation.

Détails

ID Serval
serval:BIB_C3A0F49B65F6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Proteomics reveals novel oxidative and glycolytic mechanisms in type 1 diabetic patients' skin which are normalized by kidney-pancreas transplantation.
Périodique
Plos One
Auteur(s)
Folli F., Guzzi V., Perego L., Coletta D.K., Finzi G., Placidi C., La Rosa S., Capella C., Socci C., Lauro D., Tripathy D., Jenkinson C., Paroni R., Orsenigo E., Cighetti G., Gregorini L., Staudacher C., Secchi A., Bachi A., Brownlee M., Fiorina P.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
5
Numéro
3
Pages
e9923
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Résumé
BACKGROUND: 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 delta 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.
Mots-clé
Adult, Case-Control Studies, Diabetes Mellitus, Type 1/metabolism, Diabetes Mellitus, Type 1/therapy, Female, Gene Expression Regulation, Glycolysis, Humans, Kidney Failure, Chronic/metabolism, Kidney Transplantation/methods, Male, Middle Aged, Oxygen/chemistry, Pancreas Transplantation/methods, Proteomics/methods, Skin/metabolism, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/09/2016 14:55
Dernière modification de la notice
09/05/2019 0:53
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