title: Erythrocyte caspase-3 activation and oxidative imbalance in erythrocytes and in plasma of type 2 diabetic patients.
abstract: An increased oxidative stress and a decreased life span of erythrocytes (RBCs) are reported in patients with diabetes. Aim of this study was to assess in RBCs from patients with type 2 diabetes whether downstream effector mechanisms of apoptosis, such as activation of caspase-3, is operative, and whether an iron-related oxidative imbalance, occurring inside RBCs and in plasma, could be involved in caspase-3 activation. In 26 patients with type 2 diabetes and in 12 healthy subjects, oxidative stress was evaluated by means of different markers; non-protein-bound iron, methemoglobin and glutathione were determined in RBCs, and non-protein-bound iron was also determined in plasma. Erythrocyte caspase-3 activation was evaluated by an immunosorbent enzyme assay. Arterial hypertension, demographic and standard biochemical data were also evaluated. The results show, for the first time, that type 2 diabetic RBCs put into motion caspase-3 activation, which is significantly higher than in control RBCs. Such an effector mechanism of "eryptosis" was positively correlated to blood glucose levels and to the increased plasma NPBI level. Caspase-3 activation was also positively correlated to occurrence of arterial hypertension. The results suggest that an extracellular oxidative milieu can be responsible for erythrocyte caspase-3 activation in patients with type 2 diabetes. In turn, caspase-3 activation can be envisaged as a novel mechanism which, by impairing the maintenance of erythrocyte shape and function, might contribute to the shortened life span of RBCs from patients with type 2 diabetes and to hemorheological disorders observed in these patients.
authors: Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, Via A. Moro 2, 53100, Siena, Italy.
authors: Emilia
authors: E
authors: Maellaro
authors: Silvia
authors: S
authors: Leoncini
authors: Daniele
authors: D
authors: Moretti
authors: Barbara
authors: B
authors: Del Bello
authors: Italo
authors: I
authors: Tanganelli
authors: Claudio
authors: C
authors: De Felice
authors: Lucia
authors: L
authors: Ciccoli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology; D004789:Enzyme Activation; D004912:Erythrocytes / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
chemical_list: D053148:Caspase 3