与羟基脲诱导红系祖细胞中γ-珠蛋白表达相关的有机阳离子转运体1（OCTN1）转运蛋白表达的持续增强。
Sustained enhancement of OCTN1 transporter expression in association with hydroxyurea induced γ-globin expression in erythroid progenitors.
作者信息
Walker Aisha L, Ofori-Acquah Solomon F
机构信息
Division of Pulmonary, Allergy and Critical Care Medicine, Vascular Medicine Institute, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Center for Translational and International Hematology, Vascular Medicine Institute, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Division of Pulmonary, Allergy and Critical Care Medicine, Vascular Medicine Institute, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Center for Translational and International Hematology, Vascular Medicine Institute, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Division of Hematology/Oncology, Vascular Medicine Institute, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
出版信息
Exp Hematol. 2017 Jan;45:69-73.e2. doi: 10.1016/j.exphem.2016.09.001. Epub 2016 Sep 8.
The clinical benefits of hydroxyurea (HU) treatment in patients with sickle cell disease (SCD) are due largely to increased γ-globin expression. However, mechanisms that control γ-globin expression by HU in erythroid progenitors are incompletely understood. Here, we investigated the role of two HU transporters, urea transporter B (UTB) and organic cation/carnitine transporter 1 (OCTN1), in this process. Endogenous expression of both transporters peaked toward the end of erythroid differentiation. However, unlike UTB, HU-induced OCTN1 expression correlated positively with γ-globin level and was sustained throughout the period of induction. These results highlight a potential major role for OCTN1 in promoting the efficacy of HU.
羟基脲（HU）治疗镰状细胞病（SCD）患者的临床益处很大程度上归因于γ-珠蛋白表达的增加。然而，HU在红系祖细胞中控制γ-珠蛋白表达的机制尚未完全明确。在此，我们研究了两种HU转运蛋白，尿素转运蛋白B（UTB）和有机阳离子/肉碱转运蛋白1（OCTN1）在此过程中的作用。两种转运蛋白的内源性表达在红系分化末期达到峰值。然而，与UTB不同，HU诱导的OCTN1表达与γ-珠蛋白水平呈正相关，并且在诱导期间持续存在。这些结果突出了OCTN1在促进HU疗效方面的潜在重要作用。
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