Universität zu Köln

Nader, Elie ORCID: 0000-0002-6054-2456, Grau, Marijke, Fort, Romain, Collins, Bianca, Cannas, Giovanna, Gauthier, Alexandra, Walpurgis, Katja, Martin, Cyril, Bloch, Wilhelm, Poutrel, Solene, Hot, Arnaud, Renoux, Celine, Thevis, Mario, Joly, Philippe, Romana, Marc ORCID: 0000-0002-8715-9836, Guillot, Nicolas ORCID: 0000-0003-1096-6960 and Connes, Philippe ORCID: 0000-0002-9232-0268 (2018). Hydroxyurea therapy modulates sickle cell anemia red blood cell physiology: Impact on RBC deformability, oxidative stress, nitrite levels and nitric oxide synthase signalling pathway. Nitric Oxide-Biol. Chem., 81. S. 28 - 36. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1089-8611

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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(1177) and RBC-AKT serine(473) 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(1177) and RBC-AKT serine(473) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nader, Elie UNSPECIFIED orcid.org/0000-0002-6054-2456 UNSPECIFIED Grau, Marijke UNSPECIFIED UNSPECIFIED UNSPECIFIED Fort, Romain UNSPECIFIED UNSPECIFIED UNSPECIFIED Collins, Bianca UNSPECIFIED UNSPECIFIED UNSPECIFIED Cannas, Giovanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Gauthier, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Walpurgis, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Cyril UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Poutrel, Solene UNSPECIFIED UNSPECIFIED UNSPECIFIED Hot, Arnaud UNSPECIFIED UNSPECIFIED UNSPECIFIED Renoux, Celine UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Joly, Philippe UNSPECIFIED UNSPECIFIED UNSPECIFIED Romana, Marc UNSPECIFIED orcid.org/0000-0002-8715-9836 UNSPECIFIED Guillot, Nicolas UNSPECIFIED orcid.org/0000-0003-1096-6960 UNSPECIFIED Connes, Philippe UNSPECIFIED orcid.org/0000-0002-9232-0268 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-164147
DOI:	10.1016/j.niox.2018.10.003
Journal or Publication Title:	Nitric Oxide-Biol. Chem.
Volume:	81
Page Range:	S. 28 - 36
Date:	2018
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1089-8611
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language S-NITROSYLATION; PLASMA NITRITE; IN-VITRO; RHEOLOGY; HEMOGLOBIN; OXYGEN; CHEMILUMINESCENCE; ACTIVATION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16414