Diabetes Induces p66shc Gene Expression in Human Peripheral Blood Mononuclear Cells: Relationship to Oxidative Stress

• Published in: The journal of clinical endocrinology and metabolism Vol. 90; no. 2; pp. 1130 - 1136
• Main Authors: Pagnin, Elisa, Fadini, Gianpaolo, de Toni, Renzo, Tiengo, Antonio, Calò, Lorenzo, Avogaro, Angelo
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.02.2005; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adaptor Proteins, Signal Transducing - deficiency; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; Animals; Biological and medical sciences; Cardiovascular diseases; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus - genetics; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Dinoprost - analogs & derivatives; Dinoprost - blood; Disease resistance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Humans; Leukocytes (mononuclear); Leukocytes, Mononuclear - physiology; Life span; Lymphocytes; Medical sciences; Mice; Mice, Knockout; Middle Aged; Monocytes; Oxidative stress; Oxidative Stress - physiology; Peripheral blood mononuclear cells; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - blood; RNA, Messenger - genetics; Shc Signaling Adaptor Proteins; Src Homology 2 Domain-Containing, Transforming Protein 1; Vertebrates: endocrinology; Endocrinopathy; Human; Oxidative stress; Blood cell; Mononuclear cell; Diabetes mellitus; Gene expression; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2004-1283

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 p66shc in oxidative stress-related response has been demonstrated by resistance to and reduction of oxidative stress and prolonged lifespan in p66shc−/− mice. In this study we assess p66shc gene expression in peripheral blood mononuclear cells (PBM) from type 2 diabetic patients and healthy subjects. The p66shc mRNA level was assessed using RT-PCR with two sets of primers mapping for different p66shc regions. p66shc is expressed in both monocytes and lymphocytes. The level of p66shc 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 p66shc mRNA level in PBM from type 2 diabetics (r2 = 0.47; P = 0.0284). In conclusion, diabetes induces p66shc gene expression in circulating PBM; this up-regulation in expression is significantly associated with markers of oxidative stress. p66shc gene expression in PBM may represent a useful tool to investigate the oxidative stress involved in the pathogenesis of long-term diabetic complications.