Institut de Science et d'Ingénierie Supramoléculaires, Université de Strasbourg, 8 allée Gaspard Monge, 67000 Strasbourg, France.
Chembiochem. 2010 Dec 10;11(18):2543-8. doi: 10.1002/cbic.201000499.
myo-Inositol trispyrophosphate (ITPP), a novel membrane-permeant allosteric effector of hemoglobin (Hb), enhances the regulated oxygen release capacity of red blood cells, thus counteracting the effects of hypoxia in diseases such as cancer and cardiovascular ailments. ITPP-induced shifting of the oxygen-hemoglobin equilibrium curve in red blood cells (RBCs) was inhibited by DIDS and NAP-taurine, indicating that band 3 protein, an anion transporter mainly localized on the RBC membrane, allows ITPP entry into RBCs. The maximum intracellular concentration of ITPP, determined by ion chromatography, was 5.5×10(-3) M, whereas a drop in concentration to the limit of detection was observed in NAP-taurine-treated RBCs. The dissociation constant of ITPP binding to RBC ghosts was found to be 1.72×10(-5) M. All data obtained indicate that ITPP uptake is mediated by band 3 protein and is thus highly tissue-selective towards RBCs, a feature of major importance for its potential therapeutic use.
肌醇三磷酸焦磷酸酯（ITPP）是一种新型的血红蛋白（Hb）膜通透变构效应物，可增强红细胞的氧释放调节能力，从而抵抗癌症和心血管疾病等疾病中的缺氧影响。ITPP 诱导的红细胞（RBC）氧合血红蛋白平衡曲线的移动被 DIDS 和 NAP-牛磺酸抑制，表明阴离子转运蛋白带 3 蛋白主要定位于 RBC 膜上，允许 ITPP 进入 RBC。通过离子色谱法测定的 ITPP 的最大细胞内浓度为 5.5×10(-3)M，而在用 NAP-牛磺酸处理的 RBC 中观察到浓度降至检测限以下。发现 ITPP 与 RBC 胞质体结合的解离常数为 1.72×10(-5)M。所有获得的数据表明，ITPP 的摄取是由带 3 蛋白介导的，因此对 RBC 具有高度的组织选择性，这是其潜在治疗用途的重要特征。
