Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells
Само за регистроване кориснике
2006
Аутори
Čokić, VladanBeleslin-Čokić, Bojana
Tomić, Melanija
Stojilković, Stanko S.
Noguchi, Constance T.
Schechter, Alan N.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 intracellul...ar 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.
Извор:
Blood, 2006, 108, 1, 184-191Издавач:
- Amer Soc Hematology, Washington
Финансирање / пројекти:
- Supported by the Serbian Ministry of Science and Environment (grant 145048B).
DOI: 10.1182/blood-2005-11-4454
ISSN: 0006-4971
PubMed: 16527893
WoS: 000238596900033
Scopus: 2-s2.0-33745587309
Институција/група
Institut za medicinska istraživanjaTY - 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 . .