Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo
Autor(a) principal: | |
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Data de Publicação: | 2002 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1002/ajh.10201 http://hdl.handle.net/11449/35223 |
Resumo: | Experiments were undertaken to assess the role of amifostine in the activation of latent TGFbeta1 and in the smad proteins cascade (smad 2/3, smad4, smad7), focusing on megakaryocytes, in the bone marrow irradiated in vivo. Non-irradiated megakaryocytes were negative for active TGFbeta1. Immunopositivity to active TGFbeta1 was detected in megakaryocytes 10 days after irradiation in amifostine- treated and untreated marrows. Smad 2/3 and smad 4 were strongly positive in the nucleus of megakaryocytes 10 days after irradiation. At the same time, a predominant hypocellular bone marrow with foci of hematopoiesis was observed with few megakaryocytes. An increase in the number of reticulin fibers was also seen. In amifostine-treated marrows, smad 2/3 and smad4 were not detected in the nucleus but were positive in the cytoplasm of megakaryocytes 10 days after irradiation. Coincidentally, bone marrows were cellular with megakaryocytes. Smad7 immunoexpression was detected in the cytoplasm of megakaryocytes in the non-irradiated, amifostine-treated and in the irradiated, amifostine-treated marrows. Data indicate that amifostine does not prevent latent TGFbeta1 activation in irradiated megakaryocytes. While TGFbeta1 signal transduction occurs in megakaryocytes in untreated bone marrows, it is inhibited in megakaryocytes in amifostine-treated marrows due to the induction of smad 7 activation. This is the first report showing smad 7 activation by amifostine. Our results also suggest a role for TGFbeta1 as an inhibitor of megakaryocytes in vivo. (C) 2002 Wiley-Liss, Inc. |
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Repositório Institucional da UNESP |
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Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivobone marrowamifostinegamma raysTGF betasmad cascadeExperiments were undertaken to assess the role of amifostine in the activation of latent TGFbeta1 and in the smad proteins cascade (smad 2/3, smad4, smad7), focusing on megakaryocytes, in the bone marrow irradiated in vivo. Non-irradiated megakaryocytes were negative for active TGFbeta1. Immunopositivity to active TGFbeta1 was detected in megakaryocytes 10 days after irradiation in amifostine- treated and untreated marrows. Smad 2/3 and smad 4 were strongly positive in the nucleus of megakaryocytes 10 days after irradiation. At the same time, a predominant hypocellular bone marrow with foci of hematopoiesis was observed with few megakaryocytes. An increase in the number of reticulin fibers was also seen. In amifostine-treated marrows, smad 2/3 and smad4 were not detected in the nucleus but were positive in the cytoplasm of megakaryocytes 10 days after irradiation. Coincidentally, bone marrows were cellular with megakaryocytes. Smad7 immunoexpression was detected in the cytoplasm of megakaryocytes in the non-irradiated, amifostine-treated and in the irradiated, amifostine-treated marrows. Data indicate that amifostine does not prevent latent TGFbeta1 activation in irradiated megakaryocytes. While TGFbeta1 signal transduction occurs in megakaryocytes in untreated bone marrows, it is inhibited in megakaryocytes in amifostine-treated marrows due to the induction of smad 7 activation. This is the first report showing smad 7 activation by amifostine. Our results also suggest a role for TGFbeta1 as an inhibitor of megakaryocytes in vivo. (C) 2002 Wiley-Liss, Inc.Univ Fed São Paulo, Dept Med, Div Radiotherapy, São Paulo, BrazilUniv Fed São Paulo, Dept Morphol, São Paulo, BrazilUniv Fed São Paulo, Dept Pathol, São Paulo, BrazilState Univ São Paulo, Dept Histol, São Paulo, BrazilUniv Fed São Paulo, Dept Biophys, São Paulo, BrazilState Univ São Paulo, Dept Histol, São Paulo, BrazilWiley-BlackwellUniversidade Federal de São Paulo (UNIFESP)Universidade Estadual Paulista (Unesp)Segreto, HRCFerreira, A. T.Kimura, E. T.Franco, M.Egami, M. I.Silva, MRRSegreto, R. A.2014-05-20T15:24:39Z2014-05-20T15:24:39Z2002-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article143-151application/pdfhttp://dx.doi.org/10.1002/ajh.10201American Journal of Hematology. New York: Wiley-liss, v. 71, n. 3, p. 143-151, 2002.0361-8609http://hdl.handle.net/11449/3522310.1002/ajh.10201WOS:000178973900001WOS000178973900001.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengAmerican Journal of Hematology5.3032,092info:eu-repo/semantics/openAccess2023-10-08T06:04:36Zoai:repositorio.unesp.br:11449/35223Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-10-08T06:04:36Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo |
title |
Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo |
spellingShingle |
Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo Segreto, HRC bone marrow amifostine gamma rays TGF beta smad cascade |
title_short |
Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo |
title_full |
Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo |
title_fullStr |
Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo |
title_full_unstemmed |
Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo |
title_sort |
Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo |
author |
Segreto, HRC |
author_facet |
Segreto, HRC Ferreira, A. T. Kimura, E. T. Franco, M. Egami, M. I. Silva, MRR Segreto, R. A. |
author_role |
author |
author2 |
Ferreira, A. T. Kimura, E. T. Franco, M. Egami, M. I. Silva, MRR Segreto, R. A. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Segreto, HRC Ferreira, A. T. Kimura, E. T. Franco, M. Egami, M. I. Silva, MRR Segreto, R. A. |
dc.subject.por.fl_str_mv |
bone marrow amifostine gamma rays TGF beta smad cascade |
topic |
bone marrow amifostine gamma rays TGF beta smad cascade |
description |
Experiments were undertaken to assess the role of amifostine in the activation of latent TGFbeta1 and in the smad proteins cascade (smad 2/3, smad4, smad7), focusing on megakaryocytes, in the bone marrow irradiated in vivo. Non-irradiated megakaryocytes were negative for active TGFbeta1. Immunopositivity to active TGFbeta1 was detected in megakaryocytes 10 days after irradiation in amifostine- treated and untreated marrows. Smad 2/3 and smad 4 were strongly positive in the nucleus of megakaryocytes 10 days after irradiation. At the same time, a predominant hypocellular bone marrow with foci of hematopoiesis was observed with few megakaryocytes. An increase in the number of reticulin fibers was also seen. In amifostine-treated marrows, smad 2/3 and smad4 were not detected in the nucleus but were positive in the cytoplasm of megakaryocytes 10 days after irradiation. Coincidentally, bone marrows were cellular with megakaryocytes. Smad7 immunoexpression was detected in the cytoplasm of megakaryocytes in the non-irradiated, amifostine-treated and in the irradiated, amifostine-treated marrows. Data indicate that amifostine does not prevent latent TGFbeta1 activation in irradiated megakaryocytes. While TGFbeta1 signal transduction occurs in megakaryocytes in untreated bone marrows, it is inhibited in megakaryocytes in amifostine-treated marrows due to the induction of smad 7 activation. This is the first report showing smad 7 activation by amifostine. Our results also suggest a role for TGFbeta1 as an inhibitor of megakaryocytes in vivo. (C) 2002 Wiley-Liss, Inc. |
publishDate |
2002 |
dc.date.none.fl_str_mv |
2002-11-01 2014-05-20T15:24:39Z 2014-05-20T15:24:39Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1002/ajh.10201 American Journal of Hematology. New York: Wiley-liss, v. 71, n. 3, p. 143-151, 2002. 0361-8609 http://hdl.handle.net/11449/35223 10.1002/ajh.10201 WOS:000178973900001 WOS000178973900001.pdf |
url |
http://dx.doi.org/10.1002/ajh.10201 http://hdl.handle.net/11449/35223 |
identifier_str_mv |
American Journal of Hematology. New York: Wiley-liss, v. 71, n. 3, p. 143-151, 2002. 0361-8609 10.1002/ajh.10201 WOS:000178973900001 WOS000178973900001.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
American Journal of Hematology 5.303 2,092 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
143-151 application/pdf |
dc.publisher.none.fl_str_mv |
Wiley-Blackwell |
publisher.none.fl_str_mv |
Wiley-Blackwell |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799964480722960384 |