Sustained enhancement of OCTN1 transporter expression in association with hydroxyurea induced γ-globin expression in erythroid progenitors.
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.
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. Electronic address: alw162@pitt.edu.
Aisha L
AL
Walker
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.
Solomon F
SF
Ofori-Acquah
D015415:Biomarkers; D002460:Cell Line; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D027981:Symporters; D055545:gamma-Globins / Q000235:genetics*
D015415:Biomarkers; D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; D027981:Symporters; D055545:gamma-Globins; D006918:Hydroxyurea