Morphological changes and oxidative damage in Rett Syndrome erythrocytes

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• 作者：Lucia Ciccoli^a ; ¹ ; ^{lucia.ciccoli@unisi.it} ; Claudio De Felice^b ; ¹ ; Eugenio Paccagnini^c ; Silvia Leoncini^a ; Alessandra Pecorelli^a ; Cinzia Signorini^a ; Giuseppe Belmonte^d ; Giuseppe Valacchi^e ; ^f ; Marcello Rossi^g ; Joussef Hayek^h
• 关键词：OS ; oxidative stress ; RTT ; Rett syndrome ; RBCs ; red blood cells ; NPBI ; non protein-bound iron ; F2-IsoPs ; F2-Isoprostanes ; 4-HNE PAs ; 4-HNE protein adducts ; PaO2 ; partial arterial pressure of oxygen ; 蠅-6 PUFAs ; 蠅-6 polyunsaturated fatty acids ; 蠅-3 PUFAs
• 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
• 出版年：2012
• 期刊代码：16_03044165
• 类别：bio
• 出版时间：April, 2012
• 卷：1820
• 期：4
• 页码：511-520
• 文件大小：799 K

摘要

Background

Hypoxemia and increased oxidative stress (OS) have been reported in Rett Syndrome (RTT), a genetical neurodevelopmental disorder. Although OS and hypoxemia can lead to red blood cells (RBCs) shape abnormalities, no information on RBCs morphology in RTT exists. Here, RBCs shape was evaluated in RTT patients and healthy subjects as a function of OS markers, blood oxygenation, pulmonary gas exchange, and cardio-respiratory parameters.

Methods

RBCs morphology was evaluated by Scanning Electron Microscopy. Intraerythrocyte and plasma non protein-bound iron (NPBI), esterified F₂-Isoprostanes (F₂-IsoPs), 4-HNE protein adducts (4-HNE PAs) were measured. Pulmonary oxygen gradients and PaO₂ were evaluated by gas analyzers and cardiopulmonary variables by pulse oximetry. In RTT patients these parameters were assessed before and after 蠅-3 polyunsaturated fatty acids (蠅-3 PUFAs) administration.

Results

Altered RBCs shapes (leptocytes) and increased NPBI were present in RTT, together with increased erythrocyte membrane esterified F₂-IsoPs and 4-HNE PAs. Abnormal erythrocyte shapes were related to OS markers levels, pulmonary gas exchange, PaO₂ and cardio-respiratory variables. After 蠅-3 PUFAs, a decrease of leptocytes was accompanied by a progressive increase in reversible forms of RBCs. This partial RBCs morphology rescue was related to decreased OS damage markers, improved pulmonary oxygen exchange, and cardiopulmonary physiology.

Conclusions

These findings indicate that in RTT 1) RBCs shape is altered; 2) the OS-hypoxia diad is critical in generating altered RBCs shape and membrane damage; 3) 蠅-3 PUFAs are able to partially rescue RBCs morphology and the OS-derived damage.

General significance

RBCs morphology is an important biosensor for OS imbalance and chronic hypoxemia.