Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth
Аутори
Subotički, TijanaMitrović-Ajtić, Olivera
Đikić, Dragoslava
Kovačić, Marijana
Santibanez, Juan F.
Tošić, Milica
Čokić, Vladan
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
In several systems, hydroxyurea has been shown to trigger nitric oxide (NO) release or activation of NO synthase (NOS). To elucidate this duality in its pharmacological effects, during myelosuppression, we individually examined hydroxyurea’s (NO releasing agent) and NO metabolites’ (stable NO degradation products) effects on erythroid colony growth and NOS/NO levels in mice using NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Hydroxyurea and nitrite/nitrate decreased the bone marrow cellularity that was blocked by PTIO only for the NO metabolites. Hydroxyurea inhibition of colony-forming unit-erythroid (CFU-E) formation and reticulocytes was reversed by PTIO. Moreover, hydroxyurea, through a negative feedback mechanism, reduced inducible NOS (iNOS) expressing cells in CFU-E, also prevented by PTIO. Nitrate inhibition of burst-forming units-erythroid (BFU-E) colony growth was blocked by PTIO, but not in mature CFU-E. The presented results reveal that NO rele...ase and/or production mediates the hydroxyurea inhibition of mature erythroid colony growth and the frequency of iNOS immunoreactive CFU-E.
Кључне речи:
erythroid colonies / hydroxyurea / nitrate / nitric oxide / nitric oxide synthase / nitriteИзвор:
Biomolecules, 2021, 11, 11, 1562-Издавач:
- MDPI
Финансирање / пројекти:
- HUMANE - Hydroxyurea-Mediated Activation of Nitric Oxide Synthase in Erythroid Progenitors (RS-ScienceFundRS-Promis-6061921)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200015 (Универзитет у Београду, Институт за медицинска истраживања) (RS-MESTD-inst-2020-200015)
Институција/група
Institut za medicinska istraživanjaTY - JOUR AU - Subotički, Tijana AU - Mitrović-Ajtić, Olivera AU - Đikić, Dragoslava AU - Kovačić, Marijana AU - Santibanez, Juan F. AU - Tošić, Milica AU - Čokić, Vladan PY - 2021 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1196 AB - In several systems, hydroxyurea has been shown to trigger nitric oxide (NO) release or activation of NO synthase (NOS). To elucidate this duality in its pharmacological effects, during myelosuppression, we individually examined hydroxyurea’s (NO releasing agent) and NO metabolites’ (stable NO degradation products) effects on erythroid colony growth and NOS/NO levels in mice using NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Hydroxyurea and nitrite/nitrate decreased the bone marrow cellularity that was blocked by PTIO only for the NO metabolites. Hydroxyurea inhibition of colony-forming unit-erythroid (CFU-E) formation and reticulocytes was reversed by PTIO. Moreover, hydroxyurea, through a negative feedback mechanism, reduced inducible NOS (iNOS) expressing cells in CFU-E, also prevented by PTIO. Nitrate inhibition of burst-forming units-erythroid (BFU-E) colony growth was blocked by PTIO, but not in mature CFU-E. The presented results reveal that NO release and/or production mediates the hydroxyurea inhibition of mature erythroid colony growth and the frequency of iNOS immunoreactive CFU-E. PB - MDPI T2 - Biomolecules T1 - Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth IS - 11 SP - 1562 VL - 11 DO - 10.3390/biom11111562 ER -
@article{ author = "Subotički, Tijana and Mitrović-Ajtić, Olivera and Đikić, Dragoslava and Kovačić, Marijana and Santibanez, Juan F. and Tošić, Milica and Čokić, Vladan", year = "2021", abstract = "In several systems, hydroxyurea has been shown to trigger nitric oxide (NO) release or activation of NO synthase (NOS). To elucidate this duality in its pharmacological effects, during myelosuppression, we individually examined hydroxyurea’s (NO releasing agent) and NO metabolites’ (stable NO degradation products) effects on erythroid colony growth and NOS/NO levels in mice using NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Hydroxyurea and nitrite/nitrate decreased the bone marrow cellularity that was blocked by PTIO only for the NO metabolites. Hydroxyurea inhibition of colony-forming unit-erythroid (CFU-E) formation and reticulocytes was reversed by PTIO. Moreover, hydroxyurea, through a negative feedback mechanism, reduced inducible NOS (iNOS) expressing cells in CFU-E, also prevented by PTIO. Nitrate inhibition of burst-forming units-erythroid (BFU-E) colony growth was blocked by PTIO, but not in mature CFU-E. The presented results reveal that NO release and/or production mediates the hydroxyurea inhibition of mature erythroid colony growth and the frequency of iNOS immunoreactive CFU-E.", publisher = "MDPI", journal = "Biomolecules", title = "Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth", number = "11", pages = "1562", volume = "11", doi = "10.3390/biom11111562" }
Subotički, T., Mitrović-Ajtić, O., Đikić, D., Kovačić, M., Santibanez, J. F., Tošić, M.,& Čokić, V.. (2021). Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth. in Biomolecules MDPI., 11(11), 1562. https://doi.org/10.3390/biom11111562
Subotički T, Mitrović-Ajtić O, Đikić D, Kovačić M, Santibanez JF, Tošić M, Čokić V. Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth. in Biomolecules. 2021;11(11):1562. doi:10.3390/biom11111562 .
Subotički, Tijana, Mitrović-Ajtić, Olivera, Đikić, Dragoslava, Kovačić, Marijana, Santibanez, Juan F., Tošić, Milica, Čokić, Vladan, "Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth" in Biomolecules, 11, no. 11 (2021):1562, https://doi.org/10.3390/biom11111562 . .