Red blood cell nitric oxide synthase modulates red blood cell deformability in sickle cell anemia.
Red blood cell nitric oxide synthase modulates red blood cell deformability in sickle cell anemia.
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DOI：
10.3233/ch-162042
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发表时间：
2016
影响因子：
2.1
通讯作者：
A. Mozar;P. Connes;Bianca Collins;M. Hardy-Dessources;M. Romana;Nathalie Lemonne;W. Bloch;M. Grau
中科院分区：
文献类型：
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作者：
A. Mozar;P. Connes;Bianca Collins;M. Hardy-Dessources;M. Romana;Nathalie Lemonne;W. Bloch;M. Grau
镰状细胞性贫血 (SCA) 是一种遗传性红细胞 (RBC) 疾病，其特征是红细胞变形能力显着降低。本研究旨在评估红细胞一氧化氮合酶 (RBC-NOS) 激活的调节是否会影响 SCA 中的红细胞变形能力。25 名 SCA 患者的血液在 37°C 下用磷酸盐缓冲盐水 (PBS) 或含有 1% 二甲亚砜的 PBS 作为对照、L-精氨酸或 N(5)-(1-亚氨基乙基)-L-鸟氨酸处理 1 小时(L-NIO) 直接刺激或抑制 RBC-NOS，胰岛素或渥曼青霉素通过对 PI3 激酶/Akt 通路的影响间接刺激或抑制 RBC-NOS，硝普钠 (SNP) 和 2-(4-羧基苯基)-4,4,5,5-四甲基咪唑啉-1-氧基-3-氧化物 (cPTIO) 分别作为 NO 供体和 NO 清除剂。红细胞变形能力在3 Pa下通过旋转细胞测量法测量。红细胞变形能力在胰岛素治疗后显着增加，在L-NIO和渥曼青孵育后显着降低。其他条件不影响变形能力。通过免疫组织化学在 SNP 和胰岛素处理的样品中检测到硝基酪氨酸水平显着升高，硝基酪氨酸水平是自由基生成增强的标志。这些数据表明 SCA 的红细胞变形能力可以通过 RBC-NOS 活性调节，而且氧化应激可能会损害 RBC-NOS 产生 NO 的有效性。
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.