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Red blood cell nitric oxide synthase modulates red blood cell deformability in sickle cell anemia.
Clin Hemorheol Microcirc. 2016 Nov 04; 64(1):47-53.CH

Abstract

Sickle cell anemia (SCA) is an inherited red blood cells (RBC) disorder characterized by significantly decreased RBC deformability. The present study aimed to assess whether modulation of RBC Nitric Oxide Synthase (RBC-NOS) activation could affect RBC deformability in SCA.Blood of twenty-five SCA patients was treated for 1 hour at 37°C with Phosphate Buffered Saline (PBS) or PBS containing 1% of Dimethylsulfoxyde as control, L-arginine or N(5)-(1-Iminoethyl)-L-ornithine (L-NIO) to directly stimulate or inhibit RBC-NOS, insulin or wortmannin to indirectly stimulate or inhibit RBC-NOS through their effects on the PI3 Kinase/Akt pathway, and sodium nitroprusside (SNP) and 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) as NO donor and NO scavenger, respectively. RBC deformability was measured by ektacytometry at 3 Pa.RBC deformability significantly increased after insulin treatment and significantly decreased after L-NIO and wortmannin incubation. The other conditions did not affect deformability. Significantly increased nitrotyrosine levels, a marker of enhanced free radical generation, were detected by immunohistochemistry in SNP and insulin treated samples.These data suggest that RBC deformability of SCA can be modulated by RBC-NOS activity but also that oxidative stress may impair effectiveness of RBC-NOS produced NO.

Authors+Show Affiliations

Mozar A
UMR Inserm U1134, Université des Antilles et de la Guyane, Pointe-à-Pitre, Guadeloupe, France. Laboratoire d'Excellence GR-Ex, PRES Sorbonne, Paris, France.
Connes P
UMR Inserm U1134, Université des Antilles et de la Guyane, Pointe-à-Pitre, Guadeloupe, France. Laboratoire d'Excellence GR-Ex, PRES Sorbonne, Paris, France. Laboratoire CRIS EA647, Equipe "Biologie Vasculaire et du Globule Rouge", Université Claude Bernard Lyon 1, France; Institut Universitaire de France, Paris, France.
Collins B
Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sport University, Cologne, Germany.
Hardy-Dessources MD
UMR Inserm U1134, Université des Antilles et de la Guyane, Pointe-à-Pitre, Guadeloupe, France. Laboratoire d'Excellence GR-Ex, PRES Sorbonne, Paris, France.
Romana M
UMR Inserm U1134, Université des Antilles et de la Guyane, Pointe-à-Pitre, Guadeloupe, France. Laboratoire d'Excellence GR-Ex, PRES Sorbonne, Paris, France.
Lemonne N
Unité Transversale de la Drépanocytose, Centre Hospitalier Universitaire de Pointe-à-Pitre, Pointe-à-Pitre, Guadeloupe, France.
Bloch W
Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sport University, Cologne, Germany.
Grau M
Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sport University, Cologne, Germany.

MeSH

Anemia, Sickle CellErythrocyte DeformabilityErythrocytesFemaleHumansImmunohistochemistryMaleNitric OxideOxidative Stress

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26890236

Citation

Mozar, Anaïs, et al. "Red Blood Cell Nitric Oxide Synthase Modulates Red Blood Cell Deformability in Sickle Cell Anemia." Clinical Hemorheology and Microcirculation, vol. 64, no. 1, 2016, pp. 47-53.
Mozar A, Connes P, Collins B, et al. Red blood cell nitric oxide synthase modulates red blood cell deformability in sickle cell anemia. Clin Hemorheol Microcirc. 2016;64(1):47-53.
Mozar, A., Connes, P., Collins, B., Hardy-Dessources, M. D., Romana, M., Lemonne, N., Bloch, W., & Grau, M. (2016). Red blood cell nitric oxide synthase modulates red blood cell deformability in sickle cell anemia. Clinical Hemorheology and Microcirculation, 64(1), 47-53.
Mozar A, et al. Red Blood Cell Nitric Oxide Synthase Modulates Red Blood Cell Deformability in Sickle Cell Anemia. Clin Hemorheol Microcirc. 2016 Nov 4;64(1):47-53. PubMed PMID: 26890236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Red blood cell nitric oxide synthase modulates red blood cell deformability in sickle cell anemia. AU - Mozar,Anaïs, AU - Connes,Philippe, AU - Collins,Bianca, AU - Hardy-Dessources,Marie-Dominique, AU - Romana,Marc, AU - Lemonne,Nathalie, AU - Bloch,Wilhelm, AU - Grau,Marijke, PY - 2016/2/19/pubmed PY - 2017/2/17/medline PY - 2016/2/19/entrez KW - Sickle cell disease KW - nitric oxide KW - red blood cell rheology SP - 47 EP - 53 JF - Clinical hemorheology and microcirculation JO - Clin Hemorheol Microcirc VL - 64 IS - 1 N2 - Sickle cell anemia (SCA) is an inherited red blood cells (RBC) disorder characterized by significantly decreased RBC deformability. The present study aimed to assess whether modulation of RBC Nitric Oxide Synthase (RBC-NOS) activation could affect RBC deformability in SCA.Blood of twenty-five SCA patients was treated for 1 hour at 37°C with Phosphate Buffered Saline (PBS) or PBS containing 1% of Dimethylsulfoxyde as control, L-arginine or N(5)-(1-Iminoethyl)-L-ornithine (L-NIO) to directly stimulate or inhibit RBC-NOS, insulin or wortmannin to indirectly stimulate or inhibit RBC-NOS through their effects on the PI3 Kinase/Akt pathway, and sodium nitroprusside (SNP) and 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) as NO donor and NO scavenger, respectively. RBC deformability was measured by ektacytometry at 3 Pa.RBC deformability significantly increased after insulin treatment and significantly decreased after L-NIO and wortmannin incubation. The other conditions did not affect deformability. Significantly increased nitrotyrosine levels, a marker of enhanced free radical generation, were detected by immunohistochemistry in SNP and insulin treated samples.These data suggest that RBC deformability of SCA can be modulated by RBC-NOS activity but also that oxidative stress may impair effectiveness of RBC-NOS produced NO. SN - 1875-8622 UR - https://www.unboundmedicine.com/medline/citation/26890236/Red_blood_cell_nitric_oxide_synthase_modulates_red_blood_cell_deformability_in_sickle_cell_anemia_ DB - PRIME DP - Unbound Medicine ER -