Oxygen exchange and energy metabolism in erythrocytes of Rett syndrome and their relationships with respiratory alterations

Abstract

Rett syndrome (RTT) is a neurodevelopmental disorder, mainly affecting females, which is associated to a mutation on the methyl-CpG-binding protein 2 gene. In the pathogenesis and progression of classic RTT, red blood cell (RBC) morphology has been shown to be an important biosensor for redox imbalance and chronic hypoxemia. Here we have evaluated the impact of oxidation and redox imbalance on several functional properties of RTT erythrocytes. In particular, we report for the first time a stopped-flow measurement of the kinetics of oxygen release by RBCs and the analysis of the intrinsic affinity of the hemoglobin (Hb). According to our experimental approach, RBCs from RTT patients do not show any intrinsic difference with respect to those from healthy controls neither in Hb’s oxygen-binding affinity nor in O2 exchange processes at 37 °C. Therefore, these factors do not contribute to the observed alteration of the respiratory function in RTT patients. Moreover, the energy metabolism of RBCs, from both RTT patients and controls, was evaluated by ion-pairing HPLC method and related to the level of malondialdehyde and to the oxidative radical scavenging capacity of red cells. Results have clearly confirmed significant alterations in antioxidant defense capability, adding important informations concerning the high-energy compound levels in RBCs of RTT subjects, underlying possible correlations with inflammatory tissue alterations.

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Abbreviations

RTT:

Rett syndrome

RBC:

Red blood cell

Hb:

Hemoglobin

OS:

Oxidative stress

NPBI:

Plasmatic non-protein-bound iron

Met-Hb:

Methemoglobin

CO-Hb:

Carboxyhemoglobin

MDA:

Malondialdehyde

ORAC:

Reactive oxygen species scavenging capacity

ATP:

Adenosine triphosphate

ADP:

Adenosine diphosphate

AMP:

Adenosine monophosphate

NAD+ :

Nicotinamide adenine dinucleotide

NADPH:

Nicotinamide adenine dinucleotide phosphate hydrogen

NADH:

Nicotinamide adenine dinucleotide hydrogen

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Acknowledgements

This work has been partially supported by the Federazione Medicina Sportiva Italiana (FMSI) and Associazione ProRett Siena.

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Correspondence to Chiara Ciaccio.

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Chiara Ciaccio, Donato Di Pierro contributed equally to this work.

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Ciaccio, C., Di Pierro, D., Sbardella, D. et al. Oxygen exchange and energy metabolism in erythrocytes of Rett syndrome and their relationships with respiratory alterations. Mol Cell Biochem 426, 205–213 (2017). https://doi.org/10.1007/s11010-016-2893-9

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Keywords

  • Rett syndrome
  • Erythrocytes
  • Oxidative stress
  • Hemoglobin
  • Oxygen affinity
  • Energy metabolism