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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.
Nitric Oxide. 2018 12 01; 81:28-35.NO

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.

Authors+Show Affiliations

Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, France; Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France.Molecular and Cellular Sport Medicine, Deutsche Sporthochschule Köln, Germany.Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, France; Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France; Département de Médecine Interne, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.Molecular and Cellular Sport Medicine, Deutsche Sporthochschule Köln, Germany.Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, France; Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France; Département de Médecine Interne, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, France; Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France; Institut d'Hématologie et d'Oncologie Pédiatrique, Hospices Civils de Lyon, Lyon, France.Center for Preventive Doping Research - Institute of Biochemistry, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany.Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, France; Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France.Molecular and Cellular Sport Medicine, Deutsche Sporthochschule Köln, Germany.Département de Médecine Interne, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.Département de Médecine Interne, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, France; Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France; Laboratoire de Biochimie et de Biologie Moléculaire, UF de biochimie des pathologies érythrocytaires, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Lyon, France.Center for Preventive Doping Research - Institute of Biochemistry, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany.Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, France; Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France; Laboratoire de Biochimie et de Biologie Moléculaire, UF de biochimie des pathologies érythrocytaires, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Lyon, France.Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France; UMR Inserm 1134, Hôpital Ricou, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe.Laboratoire Carmen Inserm 1060, INSA Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Villeurbanne, France.Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, France; Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France; Institut Universitaire de France, Paris, France. Electronic address: pconnes@yahoo.fr.

Pub Type(s)

Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30342855

Citation

Nader, Elie, et al. "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 : Biology and Chemistry, vol. 81, 2018, pp. 28-35.
Nader E, Grau M, Fort R, et al. 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. 2018;81:28-35.
Nader, E., Grau, M., Fort, R., Collins, B., Cannas, G., Gauthier, A., Walpurgis, K., Martin, C., Bloch, W., Poutrel, S., Hot, A., Renoux, C., Thevis, M., Joly, P., Romana, M., Guillot, N., & Connes, P. (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 : Biology and Chemistry, 81, 28-35. https://doi.org/10.1016/j.niox.2018.10.003
Nader E, et al. 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. 2018 12 1;81:28-35. PubMed PMID: 30342855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydroxyurea therapy modulates sickle cell anemia red blood cell physiology: 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, Y1 - 2018/10/19/ PY - 2018/07/11/received PY - 2018/10/16/revised PY - 2018/10/17/accepted PY - 2018/10/22/pubmed PY - 2019/2/23/medline PY - 2018/10/22/entrez KW - Deformability KW - Hydroxyurea KW - Nitric oxide KW - Oxidative stress KW - Sickle cell anaemia SP - 28 EP - 35 JF - Nitric oxide : biology and chemistry JO - Nitric Oxide VL - 81 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. SN - 1089-8611 UR - https://www.unboundmedicine.com/medline/citation/30342855/Hydroxyurea_therapy_modulates_sickle_cell_anemia_red_blood_cell_physiology:_Impact_on_RBC_deformability_oxidative_stress_nitrite_levels_and_nitric_oxide_synthase_signalling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1089-8603(18)30190-3 DB - PRIME DP - Unbound Medicine ER -