Hydroxyurea therapy modulates sickle cell anemia red blood cell physiology: Impact on RBC deformability, oxidative stress, nitrite levels and nitric oxide synthase signalling pathway

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Hydroxyurea therapy modulates sickle cell anemia red blood cell physiology : Impact on RBC deformability, oxidative stress, nitrite levels and nitric oxide synthase signalling pathway. / Nader, Elie; Grau, Marijke; Fort, Romain; Collins, Bianca; Cannas, Giovanna; Gauthier, Alexandra; Walpurgis, Katja; Martin, Cyril; Bloch, Wilhelm; Poutrel, Solène; Hot, Arnaud; Renoux, Céline; Thevis, Mario; Joly, Philippe; Romana, Marc; Guillot, Nicolas; Connes, Philippe.

in: Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society, Jahrgang 81, 01.12.2018, S. 28-35.

Publikationen: Beitrag in FachzeitschriftZeitschriftenaufsätzeForschungBegutachtung

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@article{ae7e4404e9fc481f930f7a39f9e99d05,
title = "Hydroxyurea therapy modulates sickle cell anemia red blood cell physiology: Impact on RBC deformability, oxidative stress, nitrite levels and nitric oxide synthase signalling pathway",
abstract = "Hydroxyurea (HU) has been suggested to act as a nitric oxide (NO) donor in sickle cell anemia (SCA). However, little is known about the HU NO-related effects on red blood cell (RBC) physiology and NO signalling pathway. Thirty-four patients with SCA (22 under HU treatment (HU+) and 12 without (HU-)) and 17 healthy subjects (AA) were included. RBC nitrite content, deformability and reactive oxygen species (ROS) levels were measured. RBC NO-synthase (RBC-NOS) signalling pathway was assessed by the measurement of RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation. We also investigated the in vitro effects of Sodium Nitroprusside (SNP), a NO donor, on the same parameters in SCA RBC. RBC nitrite content was higher in HU+ than in HU- and AA. RBC deformability was decreased in SCA patients compared to AA but the decrease was more pronounced in HU-. RBC ROS level was increased in SCA compared to AA but the level was higher in HU- than in HU+. RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation were decreased in HU+ compared to HU- and AA. SCA RBC treated with SNP showed increased deformability, reduced ROS content and a decrease in AKT and RBC-NOS phosphorylation. Our study suggests that HU, through its effects on foetal hemoglobin and possibly on NO delivery, would modulate RBC NO signalling pathway, RBC rheology and oxidative stress.",
keywords = "Journal Article",
author = "Elie Nader and Marijke Grau and Romain Fort and Bianca Collins and Giovanna Cannas and Alexandra Gauthier and Katja Walpurgis and Cyril Martin and Wilhelm Bloch and Sol{\`e}ne Poutrel and Arnaud Hot and C{\'e}line Renoux and Mario Thevis and Philippe Joly and Marc Romana and Nicolas Guillot and Philippe Connes",
note = "Copyright {\textcopyright} 2018 Elsevier Inc. All rights reserved.",
year = "2018",
month = dec,
day = "1",
doi = "10.1016/j.niox.2018.10.003",
language = "English",
volume = "81",
pages = "28--35",
journal = "Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society",
issn = "1089-8611",
publisher = "Academic Press Inc.",

}

RIS

TY - JOUR

T1 - Hydroxyurea therapy modulates sickle cell anemia red blood cell physiology

T2 - Impact on RBC deformability, oxidative stress, nitrite levels and nitric oxide synthase signalling pathway

AU - Nader, Elie

AU - Grau, Marijke

AU - Fort, Romain

AU - Collins, Bianca

AU - Cannas, Giovanna

AU - Gauthier, Alexandra

AU - Walpurgis, Katja

AU - Martin, Cyril

AU - Bloch, Wilhelm

AU - Poutrel, Solène

AU - Hot, Arnaud

AU - Renoux, Céline

AU - Thevis, Mario

AU - Joly, Philippe

AU - Romana, Marc

AU - Guillot, Nicolas

AU - Connes, Philippe

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Hydroxyurea (HU) has been suggested to act as a nitric oxide (NO) donor in sickle cell anemia (SCA). However, little is known about the HU NO-related effects on red blood cell (RBC) physiology and NO signalling pathway. Thirty-four patients with SCA (22 under HU treatment (HU+) and 12 without (HU-)) and 17 healthy subjects (AA) were included. RBC nitrite content, deformability and reactive oxygen species (ROS) levels were measured. RBC NO-synthase (RBC-NOS) signalling pathway was assessed by the measurement of RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation. We also investigated the in vitro effects of Sodium Nitroprusside (SNP), a NO donor, on the same parameters in SCA RBC. RBC nitrite content was higher in HU+ than in HU- and AA. RBC deformability was decreased in SCA patients compared to AA but the decrease was more pronounced in HU-. RBC ROS level was increased in SCA compared to AA but the level was higher in HU- than in HU+. RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation were decreased in HU+ compared to HU- and AA. SCA RBC treated with SNP showed increased deformability, reduced ROS content and a decrease in AKT and RBC-NOS phosphorylation. Our study suggests that HU, through its effects on foetal hemoglobin and possibly on NO delivery, would modulate RBC NO signalling pathway, RBC rheology and oxidative stress.

AB - Hydroxyurea (HU) has been suggested to act as a nitric oxide (NO) donor in sickle cell anemia (SCA). However, little is known about the HU NO-related effects on red blood cell (RBC) physiology and NO signalling pathway. Thirty-four patients with SCA (22 under HU treatment (HU+) and 12 without (HU-)) and 17 healthy subjects (AA) were included. RBC nitrite content, deformability and reactive oxygen species (ROS) levels were measured. RBC NO-synthase (RBC-NOS) signalling pathway was assessed by the measurement of RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation. We also investigated the in vitro effects of Sodium Nitroprusside (SNP), a NO donor, on the same parameters in SCA RBC. RBC nitrite content was higher in HU+ than in HU- and AA. RBC deformability was decreased in SCA patients compared to AA but the decrease was more pronounced in HU-. RBC ROS level was increased in SCA compared to AA but the level was higher in HU- than in HU+. RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation were decreased in HU+ compared to HU- and AA. SCA RBC treated with SNP showed increased deformability, reduced ROS content and a decrease in AKT and RBC-NOS phosphorylation. Our study suggests that HU, through its effects on foetal hemoglobin and possibly on NO delivery, would modulate RBC NO signalling pathway, RBC rheology and oxidative stress.

KW - Journal Article

U2 - 10.1016/j.niox.2018.10.003

DO - 10.1016/j.niox.2018.10.003

M3 - Journal articles

C2 - 30342855

VL - 81

SP - 28

EP - 35

JO - Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society

JF - Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society

SN - 1089-8611

ER -

ID: 3554324