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Erythrocyte caspase-3 activation and oxidative imbalance in erythrocytes and in plasma of type 2 diabetic patients

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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.

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Acknowledgments

This study was supported by a grant from University of Siena (Research Project entitled to L.C.).

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, Via A. Moro 2, 53100, Siena, Italy

    Emilia Maellaro, Silvia Leoncini, Daniele Moretti, Barbara Del Bello & Lucia Ciccoli

  2. Department of Odontostomatology, Diabetology Section, University of Siena, Viale Bracci, 53100, Siena, Italy

    Italo Tanganelli

  3. Neonatal Intensive Care Unit, University Hospital AOUS of Siena, Viale Bracci, 53100, Siena, Italy

    Claudio De Felice

Authors
  1. Emilia Maellaro
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  2. Silvia Leoncini
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  4. Barbara Del Bello
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  5. Italo Tanganelli
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  6. Claudio De Felice
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  7. Lucia Ciccoli
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Correspondence to Lucia Ciccoli.

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Maellaro, E., Leoncini, S., Moretti, D. et al. Erythrocyte caspase-3 activation and oxidative imbalance in erythrocytes and in plasma of type 2 diabetic patients. Acta Diabetol 50, 489–495 (2013). https://doi.org/10.1007/s00592-011-0274-0

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  • DOI: https://doi.org/10.1007/s00592-011-0274-0

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