Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin

Autores
Schattner, Mirta Ana; Pozner, Roberto Gabriel; Engelberger, I.; Gorostizaga, Alejandra Beatriz; Maugeri, Norma Iris; Gomez, Ricardo Martin; Pasqualini, Rodolfo Agustin; Torres, Oscar; Lazzari, María Ángela
Año de publicación
2001
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The present study investigated the effect of nitric oxide (NO) on megakaryocyte (Mk) proliferation induced by thrombopoietin (TPO). Low-density mononuclear cells (MNCs) and CD34+ cells from human bone marrow (BM) were cultured in liquid medium in the presence of sodium nitroprusside (SNP) or (Z)-1-[2-(aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA/NO) and then stimulated with TPO. Mk number decreased in both NO donors, as identified by flow cytometry 11 to 13 days after TPO stimulation. Nitrite, cyanide, or the carrier molecule DETA failed to reproduce the inhibition caused by NO donors. When CD34+ cells were treated with DETA/NO, the inhibition of Mk growth was even more pronounced than that in MNCs. Failure of the guanosine 3′,5′-cyclic monophosphate (cGMP) analog 8-bromoguanosine 3′,5′-cyclic monophosphate (8-Br-cGMP) to inhibit Mk proliferation suggests that cGMP is not involved in Mk suppression mediated by NO. On the other hand, DNA analysis by flow cytometry showed that apoptosis of CD34+ cells and Mks seemed to be at least one of the mechanisms associated with the cytotoxic DETA/NO effect. Stimulation of MNCs or CD34+ cells with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) increased endogenous NO levels and suppressed Mk growth. Treatment with NO synthesis inhibitors such as L-NG-monomethyl arginine (L-NMMA) or L-NG-nitroarginine methyl ester hydrochloride (L-NAME) partially reversed Mk growth inhibition induced by TNF-α and IFN-γ, although increased NO levels returned to normal values. The results presented here strongly indicate that NO regulates the growth of Mks induced by TPO by a direct effect on both progenitors and mature Mks.
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Engelberger, I.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Gorostizaga, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Maugeri, Norma Iris. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Gomez, Ricardo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Pasqualini, Rodolfo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Torres, Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Lazzari, María Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/55318
Acceder
id CONICETDig_ec3280a7e0c6e75c3d1e5e2d0c9ad49e
oai_identifier_str oai:ri.conicet.gov.ar:11336/55318
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effect of nitric oxide on megakaryocyte growth induced by thrombopoietinSchattner, Mirta AnaPozner, Roberto GabrielEngelberger, I.Gorostizaga, Alejandra BeatrizMaugeri, Norma IrisGomez, Ricardo MartinPasqualini, Rodolfo AgustinTorres, OscarLazzari, María Ángelahttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3The present study investigated the effect of nitric oxide (NO) on megakaryocyte (Mk) proliferation induced by thrombopoietin (TPO). Low-density mononuclear cells (MNCs) and CD34+ cells from human bone marrow (BM) were cultured in liquid medium in the presence of sodium nitroprusside (SNP) or (Z)-1-[2-(aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA/NO) and then stimulated with TPO. Mk number decreased in both NO donors, as identified by flow cytometry 11 to 13 days after TPO stimulation. Nitrite, cyanide, or the carrier molecule DETA failed to reproduce the inhibition caused by NO donors. When CD34+ cells were treated with DETA/NO, the inhibition of Mk growth was even more pronounced than that in MNCs. Failure of the guanosine 3′,5′-cyclic monophosphate (cGMP) analog 8-bromoguanosine 3′,5′-cyclic monophosphate (8-Br-cGMP) to inhibit Mk proliferation suggests that cGMP is not involved in Mk suppression mediated by NO. On the other hand, DNA analysis by flow cytometry showed that apoptosis of CD34+ cells and Mks seemed to be at least one of the mechanisms associated with the cytotoxic DETA/NO effect. Stimulation of MNCs or CD34+ cells with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) increased endogenous NO levels and suppressed Mk growth. Treatment with NO synthesis inhibitors such as L-NG-monomethyl arginine (L-NMMA) or L-NG-nitroarginine methyl ester hydrochloride (L-NAME) partially reversed Mk growth inhibition induced by TNF-α and IFN-γ, although increased NO levels returned to normal values. The results presented here strongly indicate that NO regulates the growth of Mks induced by TPO by a direct effect on both progenitors and mature Mks.Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Engelberger, I.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Gorostizaga, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Maugeri, Norma Iris. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Gomez, Ricardo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Pasqualini, Rodolfo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Torres, Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Lazzari, María Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaElsevier2001-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/55318Schattner, Mirta Ana; Pozner, Roberto Gabriel; Engelberger, I.; Gorostizaga, Alejandra Beatriz; Maugeri, Norma Iris; et al.; Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin; Elsevier; The Journal Of Laboratory And Clinical Medicine.; 137; 4; 4-2001; 261-2690022-2143CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1067/mlc.2001.113659info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022214301092964info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:38:41Zoai:ri.conicet.gov.ar:11336/55318instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:38:41.461CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin
title Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin
spellingShingle Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin
Schattner, Mirta Ana
title_short Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin
title_full Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin
title_fullStr Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin
title_full_unstemmed Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin
title_sort Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin
dc.creator.none.fl_str_mv Schattner, Mirta Ana
Pozner, Roberto Gabriel
Engelberger, I.
Gorostizaga, Alejandra Beatriz
Maugeri, Norma Iris
Gomez, Ricardo Martin
Pasqualini, Rodolfo Agustin
Torres, Oscar
Lazzari, María Ángela
author Schattner, Mirta Ana
author_facet Schattner, Mirta Ana
Pozner, Roberto Gabriel
Engelberger, I.
Gorostizaga, Alejandra Beatriz
Maugeri, Norma Iris
Gomez, Ricardo Martin
Pasqualini, Rodolfo Agustin
Torres, Oscar
Lazzari, María Ángela
author_role author
author2 Pozner, Roberto Gabriel
Engelberger, I.
Gorostizaga, Alejandra Beatriz
Maugeri, Norma Iris
Gomez, Ricardo Martin
Pasqualini, Rodolfo Agustin
Torres, Oscar
Lazzari, María Ángela
author2_role author
author
author
author
author
author
author
author
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The present study investigated the effect of nitric oxide (NO) on megakaryocyte (Mk) proliferation induced by thrombopoietin (TPO). Low-density mononuclear cells (MNCs) and CD34+ cells from human bone marrow (BM) were cultured in liquid medium in the presence of sodium nitroprusside (SNP) or (Z)-1-[2-(aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA/NO) and then stimulated with TPO. Mk number decreased in both NO donors, as identified by flow cytometry 11 to 13 days after TPO stimulation. Nitrite, cyanide, or the carrier molecule DETA failed to reproduce the inhibition caused by NO donors. When CD34+ cells were treated with DETA/NO, the inhibition of Mk growth was even more pronounced than that in MNCs. Failure of the guanosine 3′,5′-cyclic monophosphate (cGMP) analog 8-bromoguanosine 3′,5′-cyclic monophosphate (8-Br-cGMP) to inhibit Mk proliferation suggests that cGMP is not involved in Mk suppression mediated by NO. On the other hand, DNA analysis by flow cytometry showed that apoptosis of CD34+ cells and Mks seemed to be at least one of the mechanisms associated with the cytotoxic DETA/NO effect. Stimulation of MNCs or CD34+ cells with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) increased endogenous NO levels and suppressed Mk growth. Treatment with NO synthesis inhibitors such as L-NG-monomethyl arginine (L-NMMA) or L-NG-nitroarginine methyl ester hydrochloride (L-NAME) partially reversed Mk growth inhibition induced by TNF-α and IFN-γ, although increased NO levels returned to normal values. The results presented here strongly indicate that NO regulates the growth of Mks induced by TPO by a direct effect on both progenitors and mature Mks.
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Engelberger, I.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Gorostizaga, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Maugeri, Norma Iris. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Gomez, Ricardo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Pasqualini, Rodolfo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Torres, Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Lazzari, María Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
description The present study investigated the effect of nitric oxide (NO) on megakaryocyte (Mk) proliferation induced by thrombopoietin (TPO). Low-density mononuclear cells (MNCs) and CD34+ cells from human bone marrow (BM) were cultured in liquid medium in the presence of sodium nitroprusside (SNP) or (Z)-1-[2-(aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA/NO) and then stimulated with TPO. Mk number decreased in both NO donors, as identified by flow cytometry 11 to 13 days after TPO stimulation. Nitrite, cyanide, or the carrier molecule DETA failed to reproduce the inhibition caused by NO donors. When CD34+ cells were treated with DETA/NO, the inhibition of Mk growth was even more pronounced than that in MNCs. Failure of the guanosine 3′,5′-cyclic monophosphate (cGMP) analog 8-bromoguanosine 3′,5′-cyclic monophosphate (8-Br-cGMP) to inhibit Mk proliferation suggests that cGMP is not involved in Mk suppression mediated by NO. On the other hand, DNA analysis by flow cytometry showed that apoptosis of CD34+ cells and Mks seemed to be at least one of the mechanisms associated with the cytotoxic DETA/NO effect. Stimulation of MNCs or CD34+ cells with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) increased endogenous NO levels and suppressed Mk growth. Treatment with NO synthesis inhibitors such as L-NG-monomethyl arginine (L-NMMA) or L-NG-nitroarginine methyl ester hydrochloride (L-NAME) partially reversed Mk growth inhibition induced by TNF-α and IFN-γ, although increased NO levels returned to normal values. The results presented here strongly indicate that NO regulates the growth of Mks induced by TPO by a direct effect on both progenitors and mature Mks.
publishDate 2001
dc.date.none.fl_str_mv 2001-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/55318
Schattner, Mirta Ana; Pozner, Roberto Gabriel; Engelberger, I.; Gorostizaga, Alejandra Beatriz; Maugeri, Norma Iris; et al.; Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin; Elsevier; The Journal Of Laboratory And Clinical Medicine.; 137; 4; 4-2001; 261-269
0022-2143
CONICET Digital
CONICET
url http://hdl.handle.net/11336/55318
identifier_str_mv Schattner, Mirta Ana; Pozner, Roberto Gabriel; Engelberger, I.; Gorostizaga, Alejandra Beatriz; Maugeri, Norma Iris; et al.; Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin; Elsevier; The Journal Of Laboratory And Clinical Medicine.; 137; 4; 4-2001; 261-269
0022-2143
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1067/mlc.2001.113659
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022214301092964
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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