TY  - JOUR
AU  - Čokić, Vladan
AU  - Beleslin-Čokić, Bojana
AU  - Tomić, Melanija
AU  - Stojilković, Stanko S.
AU  - Noguchi, Constance T.
AU  - Schechter, Alan N.
PY  - 2006
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/150
AB  - Hydroxyurea is a cell-cycle-specific drug that has been used to treat myeloproliferative diseases and sickle cell anemia. We have recently shown that hydroxyurea, like nitric oxide (NO)-donor compounds, increased cGMP levels in human erythroid cells. We show now that hydroxyurea increases endothelial-cell production of NO; this induction of NO in human umbilical vein endothelial cells (HUVECs) and human bone marrow endothelial cell line (TrHBMEC) is blocked by competitive inhibitors of NO synthase (NOS), such as N-G-nitro-L-arginine-methyl ester (L-NAME) and N-G-nitro-L-arginine. It is dependent on cAMP-dependent protein kinase (PKA) and protein kinase B (PKB/Akt) activity. We found that hydroxyurea dose- and time-dependently induced rapid and transient phosphorylation of eNOS at Ser1177 in a PKA-dependent manner; inhibitors of PKB/Akt could partially abrogate this effect. In addition, hydroxyurea induced cAMP and cGMP levels in a dose-dependent manner, as well as levels of intracellular calcium in HUVECs. These studies established an additional mechanism by which rapid and sustained effects of hydroxyurea may affect cellular NO levels and perhaps enhance the effect of NO in myeloproliferative diseases.
PB  - Amer Soc Hematology, Washington
T2  - Blood
T1  - Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells
EP  - 191
IS  - 1
SP  - 184
VL  - 108
DO  - 10.1182/blood-2005-11-4454
ER  - 

@article{
author = "Čokić, Vladan and Beleslin-Čokić, Bojana and Tomić, Melanija and Stojilković, Stanko S. and Noguchi, Constance T. and Schechter, Alan N.",
year = "2006",
abstract = "Hydroxyurea is a cell-cycle-specific drug that has been used to treat myeloproliferative diseases and sickle cell anemia. We have recently shown that hydroxyurea, like nitric oxide (NO)-donor compounds, increased cGMP levels in human erythroid cells. We show now that hydroxyurea increases endothelial-cell production of NO; this induction of NO in human umbilical vein endothelial cells (HUVECs) and human bone marrow endothelial cell line (TrHBMEC) is blocked by competitive inhibitors of NO synthase (NOS), such as N-G-nitro-L-arginine-methyl ester (L-NAME) and N-G-nitro-L-arginine. It is dependent on cAMP-dependent protein kinase (PKA) and protein kinase B (PKB/Akt) activity. We found that hydroxyurea dose- and time-dependently induced rapid and transient phosphorylation of eNOS at Ser1177 in a PKA-dependent manner; inhibitors of PKB/Akt could partially abrogate this effect. In addition, hydroxyurea induced cAMP and cGMP levels in a dose-dependent manner, as well as levels of intracellular calcium in HUVECs. These studies established an additional mechanism by which rapid and sustained effects of hydroxyurea may affect cellular NO levels and perhaps enhance the effect of NO in myeloproliferative diseases.",
publisher = "Amer Soc Hematology, Washington",
journal = "Blood",
title = "Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells",
pages = "191-184",
number = "1",
volume = "108",
doi = "10.1182/blood-2005-11-4454"
}

Čokić, V., Beleslin-Čokić, B., Tomić, M., Stojilković, S. S., Noguchi, C. T.,& Schechter, A. N.. (2006). Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells. in Blood
Amer Soc Hematology, Washington., 108(1), 184-191.
https://doi.org/10.1182/blood-2005-11-4454

Čokić V, Beleslin-Čokić B, Tomić M, Stojilković SS, Noguchi CT, Schechter AN. Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells. in Blood. 2006;108(1):184-191.
doi:10.1182/blood-2005-11-4454 .

Čokić, Vladan, Beleslin-Čokić, Bojana, Tomić, Melanija, Stojilković, Stanko S., Noguchi, Constance T., Schechter, Alan N., "Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells" in Blood, 108, no. 1 (2006):184-191,
https://doi.org/10.1182/blood-2005-11-4454 . .