Research output: Contribution to journal › Journal articles › Research › peer-review
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, Vol. 81, 01.12.2018, p. 28-35.Research output: Contribution to journal › Journal articles › Research › peer-review
}
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