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Combined effects of arginine and hydroxyurea on BFU-E derived colony growth and HbF synthesis in erythroid progenitors isolated from sickle cell blood
Corresponding Author(s) : B. S. Baliga
bbaliga@usouthal.edu
Cellular and Molecular Biology,
Vol. 56 No. 3: General Papers
Abstract
Hydroxyurea (HU) increases HbF synthesis in sickle cell disease (SCD). Recent studies suggest HU-induced HbF synthesis is mediated through a NO-cGMP pathway. Since arginine is the main precursor of NO, we investigated the effects of arginine and HU mixtures on HbF synthesis and burst forming unit erythroid (BFU-E) proliferation. Mixtures of HU (0, 15, 25, 100µM) and arginine (0, 25, 50, and 100µM) resulting in optimal HbF synthesis and minimal HU-induced cytotoxicity in erythroid progenitors were determined. HU dose-dependently attenuated growth of BFU-E colonies and stimulated HbF synthesis. In contrast, arginine dose-dependently increased BFU-E colonies without affecting HbF synthesis. Furthermore, arginine at concentrations >100µM in combination with varying concentrations of HU, decreased HbF synthesis compared to HU controls. HU, 15-25µM, in combination with 25-50µM arginine not only minimized cytotoxicity, but also increased HbF synthesis when compared with HU controls. NG-nitro-L-arginine-methyl ester (L-NAME; 100µM), a nitric oxide synthase inhibitor, attenuated the effects of HU+arginine on HbF synthesis compared to HU and HU+arginine controls. These results suggest HU+arginine-induced HbF synthesis in human erythroid progenitors is NO dependent. The synergistic effect on HbF synthesis seen with combinations HU+arginine is an important observation in understanding potential therapeutic uses of HU and arginine.
Keywords
Nitric oxide-cGMP pathway
NG-nitro-L-arginine-methyl ester
cytostatic effect
proliferative effect.
Baliga, B. S., Haynes Jr, J., Obiako, B., & Mishra, N. (2010). Combined effects of arginine and hydroxyurea on BFU-E derived colony growth and HbF synthesis in erythroid progenitors isolated from sickle cell blood. Cellular and Molecular Biology, 56(3), 1290–98. Retrieved from https://mail.cellmolbiol.org/index.php/CMB/article/view/976
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