Poly(ADP-ribosylated) proteins in mononuclear cells from patients with type 2 diabetes identified by proteomic studies

Abstract. Aims In diabetes, hyperglycemia increases reactive oxygen species that induce DNA damage and poly(ADP-ribose) polymerase activation. The aim of this study is to characterize the proteomic profile and the role of poly(-ADP-ribosylation) in patients with type 2 diabetes. Methods A proteomic platform based on 2DE and MALDI-ToF spectrometry was applied to peripheral blood mononuclear cells obtained from two different cohorts in which diabetic (n = 14) and normoglycemic patients (n = 11) were enrolled. Results Proteomic maps identified WD repeat protein, 78-kDa glucose-regulated protein precursor and myosin regulatory light chain 2, as unique proteins in diabetic patients; vimentin, elongation factor 2, annexin A1, glutathione S-transferase P, moesin and cofilin-1 as unique in the normoglycemic; and calreticulin, rho GDP-dissociation inhibitor 2, protein disulfide isomerase and tropomyosin alpha-4-chain as differentially expressed between the two cohorts. An enrichment in PARylation in diabetic patients was observed in particular, affecting GAPDH and a-Enolase leading to a decrease in their enzymatic activity. Conclusions As the GAPDH and a-Enolase are involved in energy metabolism, protein synthesis and DNA repair, loss of their function or change in their activity can significantly contribute to the molecular mechanisms responsible for the development of type 2 diabetes. These data along with the proteomic profile associated with the disease may provide new insight into the pathophysiology of type 2 diabetes.