This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pagnin, E. Articles by Avogaro, A. Search for Related Content PubMed PubMed Citation Articles by Pagnin, E. Articles by Avogaro, A. Related Collections Diabetes and Insulin

Diabetes Induces p66^shc Gene Expression in Human Peripheral Blood Mononuclear Cells: Relationship to Oxidative Stress

Department of Clinical and Experimental Medicine, University of Padova School of Medicine, 35128 Padova, Italy

Address all correspondence and requests for reprints to: Dr. Angelo Avogaro, Cattedra di Malattie del Metabolismo, Università degli Studi di Padova, Via Giustiniani 2, 35128 Padova, Italy. E-mail: angelo.avogaro{at}unipd.it.

Oxidative stress plays a role in cardiovascular dysfunction. This is of interest in diabetes, a clinical condition characterized by oxidative stress and increased prevalence of cardiovascular disease. The role of p66^shc in oxidative stress-related response has been demonstrated by resistance to and reduction of oxidative stress and prolonged lifespan in p66^shc–/– mice. In this study we assess p66^shc gene expression in peripheral blood mononuclear cells (PBM) from type 2 diabetic patients and healthy subjects. The p66^shc mRNA level was assessed using RT-PCR with two sets of primers mapping for different p66^shc regions. p66^shc is expressed in both monocytes and lymphocytes. The level of p66^shc mRNA was significantly higher in type 2 diabetic patients compared with controls (0.38 ± 0.07 densitometric units vs. 0.13 ± 0.08; P < 0.0001). In addition, total plasma 8-isoprostane levels, a marker of oxidative stress, were higher in type 2 diabetics (0.72 ± 0.04 ng/ml) than in normal subjects (0.43 ± 0.04, P < 0.001) and were significantly correlated to the p66^shc mRNA level in PBM from type 2 diabetics (r² = 0.47; P = 0.0284). In conclusion, diabetes induces p66^shc gene expression in circulating PBM; this up-regulation in expression is significantly associated with markers of oxidative stress. p66^shc gene expression in PBM may represent a useful tool to investigate the oxidative stress involved in the pathogenesis of long-term diabetic complications.

This article has been cited by other articles:

				V. Di Stefano, C. Cencioni, G. Zaccagnini, A. Magenta, M. C. Capogrossi, and F. Martelli p66ShcA modulates oxidative stress and survival of endothelial progenitor cells in response to high glucose Cardiovasc Res, June 1, 2009; 82(3): 421 - 429. [Abstract] [Full Text] [PDF]

				J. Sainz and M. Sata When p66ShcA is away, mice EPCs sweetly play Cardiovasc Res, June 1, 2009; 82(3): 388 - 389. [Full Text] [PDF]

				G. G. Camici, F. Cosentino, F. C. Tanner, and T. F. Luscher The role of p66Shc deletion in age-associated arterial dysfunction and disease states J Appl Physiol, November 1, 2008; 105(5): 1628 - 1631. [Abstract] [Full Text] [PDF]

				M. Gertz, F. Fischer, D. Wolters, and C. Steegborn Activation of the lifespan regulator p66Shc through reversible disulfide bond formation PNAS, April 15, 2008; 105(15): 5705 - 5709. [Abstract] [Full Text] [PDF]

				F. Cosentino, P. Francia, G. G. Camici, P. G. Pelicci, M. Volpe, and T. F. Luscher Final Common Molecular Pathways of Aging and Cardiovascular Disease: Role of the p66Shc Protein Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 622 - 628. [Abstract] [Full Text] [PDF]

				H.-Z. Pan, H. Zhang, D. Chang, H. Li, and H. Sui The change of oxidative stress products in diabetes mellitus and diabetic retinopathy Br. J. Ophthalmol., April 1, 2008; 92(4): 548 - 551. [Abstract] [Full Text] [PDF]

				W. Cai, J. C. He, L. Zhu, X. Chen, G. E. Striker, and H. Vlassara AGE-receptor-1 counteracts cellular oxidant stress induced by AGEs via negative regulation of p66shc-dependent FKHRL1 phosphorylation Am J Physiol Cell Physiol, January 1, 2008; 294(1): C145 - C152. [Abstract] [Full Text] [PDF]

				G. P. Fadini, S. Sartore, C. Agostini, and A. Avogaro Significance of Endothelial Progenitor Cells in Subjects With Diabetes Diabetes Care, May 1, 2007; 30(5): 1305 - 1313. [Full Text] [PDF]

				G. G. Camici, M. Schiavoni, P. Francia, M. Bachschmid, I. Martin-Padura, M. Hersberger, F. C. Tanner, P. Pelicci, M. Volpe, P. Anversa, et al. Genetic deletion of p66Shc adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress PNAS, March 20, 2007; 104(12): 5217 - 5222. [Abstract] [Full Text] [PDF]

				G. P. Fadini, S. Sartore, M. Albiero, I. Baesso, E. Murphy, M. Menegolo, F. Grego, S. Vigili de Kreutzenberg, A. Tiengo, C. Agostini, et al. Number and Function of Endothelial Progenitor Cells as a Marker of Severity for Diabetic Vasculopathy Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 2140 - 2146. [Abstract] [Full Text] [PDF]

				S. Menini, L. Amadio, G. Oddi, C. Ricci, C. Pesce, F. Pugliese, M. Giorgio, E. Migliaccio, P. Pelicci, C. Iacobini, et al. Deletion of p66Shc Longevity Gene Protects Against Experimental Diabetic Glomerulopathy by Preventing Diabetes-Induced Oxidative Stress Diabetes, June 1, 2006; 55(6): 1642 - 1650. [Abstract] [Full Text] [PDF]

				P. A. Davis, E. Pagnin, A. Semplicini, A. Avogaro, and L. A. Calo Insulin Signaling, Glucose Metabolism, and the Angiotensin II Signaling System: Studies in Bartter's/Gitelman's syndromes Diabetes Care, February 1, 2006; 29(2): 469 - 471. [Full Text] [PDF]