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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.
- Source :
-
Nitric oxide : biology and chemistry [Nitric Oxide] 2018 Dec 01; Vol. 81, pp. 28-35. Date of Electronic Publication: 2018 Oct 19. - Publication Year :
- 2018
-
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 serine <superscript>1177</superscript> and RBC-AKT serine <superscript>473</superscript> 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 serine <superscript>1177</superscript> and RBC-AKT serine <superscript>473</superscript> 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.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Erythrocytes physiology
Female
Humans
Male
Nitric Oxide blood
Nitric Oxide Synthase metabolism
Nitroprusside pharmacology
Oxidative Stress drug effects
Phosphorylation drug effects
Proto-Oncogene Proteins c-akt metabolism
Reactive Oxygen Species blood
Signal Transduction drug effects
Anemia, Sickle Cell drug therapy
Erythrocyte Deformability drug effects
Erythrocytes drug effects
Hydroxyurea pharmacology
Nitrites blood
Subjects
Details
- Language :
- English
- ISSN :
- 1089-8611
- Volume :
- 81
- Database :
- MEDLINE
- Journal :
- Nitric oxide : biology and chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30342855
- Full Text :
- https://doi.org/10.1016/j.niox.2018.10.003