Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth

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 degrad...

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Autores principales:	Tijana Subotički, Olivera Mitrović Ajtić, Dragoslava Djikić, Marijana Kovačić, Juan F. Santibanez, Milica Tošić, Vladan P. Čokić
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hydroxyurea nitric oxide erythroid colonies nitric oxide synthase nitrite nitrate Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d9113f8dbc9b4b628f010db3de4ea6ef
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id	oai:doaj.org-article:d9113f8dbc9b4b628f010db3de4ea6ef
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spelling	oai:doaj.org-article:d9113f8dbc9b4b628f010db3de4ea6ef2021-11-25T16:51:53ZNitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth10.3390/biom111115622218-273Xhttps://doaj.org/article/d9113f8dbc9b4b628f010db3de4ea6ef2021-10-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1562https://doaj.org/toc/2218-273XIn 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.Tijana SubotičkiOlivera Mitrović AjtićDragoslava DjikićMarijana KovačićJuan F. SantibanezMilica TošićVladan P. ČokićMDPI AGarticlehydroxyureanitric oxideerythroid coloniesnitric oxide synthasenitritenitrateMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1562, p 1562 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hydroxyurea nitric oxide erythroid colonies nitric oxide synthase nitrite nitrate Microbiology QR1-502
spellingShingle	hydroxyurea nitric oxide erythroid colonies nitric oxide synthase nitrite nitrate Microbiology QR1-502 Tijana Subotički Olivera Mitrović Ajtić Dragoslava Djikić Marijana Kovačić Juan F. Santibanez Milica Tošić Vladan P. Čokić Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth
description	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.
format	article
author	Tijana Subotički Olivera Mitrović Ajtić Dragoslava Djikić Marijana Kovačić Juan F. Santibanez Milica Tošić Vladan P. Čokić
author_facet	Tijana Subotički Olivera Mitrović Ajtić Dragoslava Djikić Marijana Kovačić Juan F. Santibanez Milica Tošić Vladan P. Čokić
author_sort	Tijana Subotički
title	Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth
title_short	Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth
title_full	Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth
title_fullStr	Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth
title_full_unstemmed	Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth
title_sort	nitric oxide mediation in hydroxyurea and nitric oxide metabolites’ inhibition of erythroid progenitor growth
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d9113f8dbc9b4b628f010db3de4ea6ef
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Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth

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