Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications

Autores
Chiappini, Florencia Ana; Pontillo, Carolina Andrea; Randi, Andrea Silvana; Álvarez, Laura; Kleiman, Diana Leonor
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hexachlorobenzene (HCB) is an organochlorine pesticide widely distributed in the environment. In this study we have demonstrated that HCB induced loss of cell viability and alterations in cell cycle regulation in FRTL-5 rat thyroid cells. Analysis of cell cycle distribution by flow cytometric analysis demonstrated that HCB induced cell cycle arrest at G2/M and at G0/G1 phase, inhibiting cell cycle progression at the G1/S phase, after 24 h and 72 h of treatment. HCB-treatment resulted in an increase in transforming growth factor-beta (TGF-β1) mRNA levels, a negative regulator of cell growth in thyroid epithelial cells. Time-dependent studies showed that both cytosolic and nuclear p27 protein levels were increased by 5 μM HCB. After 24 h of treatment, total p27 in whole cells lysate was increased. Dose-dependent studies, demonstrated that HCB (0.005, 0.05, 0.5 and 5 μM) increased p27, both in the cytosol and nucleus. HCB (5 μM) induced a concomitant decrease in nuclear cyclin D1 protein levels, in a time-dependent manner. We have also demonstrated that TGF-β1 Smad signaling is involved in HCB-induced alterations of p27 and cyclin D1 protein levels. On the other hand, ERK1/2 activation is not involved in the alteration of cell cycle regulatory proteins.
Fil: Chiappini, Florencia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Pontillo, Carolina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Álvarez, Laura. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Kleiman, Diana Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Materia
Frtl-5 Cells
Hexachlorobenzene
Tgf-Β1
Cell Cycle
P27
Cyclin D1
Erk1/2
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/13812
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/13812
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modificationsChiappini, Florencia AnaPontillo, Carolina AndreaRandi, Andrea SilvanaÁlvarez, LauraKleiman, Diana LeonorFrtl-5 CellsHexachlorobenzeneTgf-Β1Cell CycleP27Cyclin D1Erk1/2https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Hexachlorobenzene (HCB) is an organochlorine pesticide widely distributed in the environment. In this study we have demonstrated that HCB induced loss of cell viability and alterations in cell cycle regulation in FRTL-5 rat thyroid cells. Analysis of cell cycle distribution by flow cytometric analysis demonstrated that HCB induced cell cycle arrest at G2/M and at G0/G1 phase, inhibiting cell cycle progression at the G1/S phase, after 24 h and 72 h of treatment. HCB-treatment resulted in an increase in transforming growth factor-beta (TGF-β1) mRNA levels, a negative regulator of cell growth in thyroid epithelial cells. Time-dependent studies showed that both cytosolic and nuclear p27 protein levels were increased by 5 μM HCB. After 24 h of treatment, total p27 in whole cells lysate was increased. Dose-dependent studies, demonstrated that HCB (0.005, 0.05, 0.5 and 5 μM) increased p27, both in the cytosol and nucleus. HCB (5 μM) induced a concomitant decrease in nuclear cyclin D1 protein levels, in a time-dependent manner. We have also demonstrated that TGF-β1 Smad signaling is involved in HCB-induced alterations of p27 and cyclin D1 protein levels. On the other hand, ERK1/2 activation is not involved in the alteration of cell cycle regulatory proteins.Fil: Chiappini, Florencia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Pontillo, Carolina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Álvarez, Laura. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Kleiman, Diana Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaElsevier2014-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/13812Chiappini, Florencia Ana; Pontillo, Carolina Andrea; Randi, Andrea Silvana; Álvarez, Laura; Kleiman, Diana Leonor; Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications; Elsevier; Toxicology Letters; 230; 1; 10-2014; 1-90378-4274enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0378427414012077info:eu-repo/semantics/altIdentifier/doi/10.1016/j.toxlet.2014.08.002info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:11:45Zoai:ri.conicet.gov.ar:11336/13812instacron: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:34982025-09-29 10:11:45.682CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications
title Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications
spellingShingle Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications
Chiappini, Florencia Ana
Frtl-5 Cells
Hexachlorobenzene
Tgf-Β1
Cell Cycle
P27
Cyclin D1
Erk1/2
title_short Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications
title_full Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications
title_fullStr Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications
title_full_unstemmed Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications
title_sort Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications
dc.creator.none.fl_str_mv Chiappini, Florencia Ana
Pontillo, Carolina Andrea
Randi, Andrea Silvana
Álvarez, Laura
Kleiman, Diana Leonor
author Chiappini, Florencia Ana
author_facet Chiappini, Florencia Ana
Pontillo, Carolina Andrea
Randi, Andrea Silvana
Álvarez, Laura
Kleiman, Diana Leonor
author_role author
author2 Pontillo, Carolina Andrea
Randi, Andrea Silvana
Álvarez, Laura
Kleiman, Diana Leonor
author2_role author
author
author
author
dc.subject.none.fl_str_mv Frtl-5 Cells
Hexachlorobenzene
Tgf-Β1
Cell Cycle
P27
Cyclin D1
Erk1/2
topic Frtl-5 Cells
Hexachlorobenzene
Tgf-Β1
Cell Cycle
P27
Cyclin D1
Erk1/2
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hexachlorobenzene (HCB) is an organochlorine pesticide widely distributed in the environment. In this study we have demonstrated that HCB induced loss of cell viability and alterations in cell cycle regulation in FRTL-5 rat thyroid cells. Analysis of cell cycle distribution by flow cytometric analysis demonstrated that HCB induced cell cycle arrest at G2/M and at G0/G1 phase, inhibiting cell cycle progression at the G1/S phase, after 24 h and 72 h of treatment. HCB-treatment resulted in an increase in transforming growth factor-beta (TGF-β1) mRNA levels, a negative regulator of cell growth in thyroid epithelial cells. Time-dependent studies showed that both cytosolic and nuclear p27 protein levels were increased by 5 μM HCB. After 24 h of treatment, total p27 in whole cells lysate was increased. Dose-dependent studies, demonstrated that HCB (0.005, 0.05, 0.5 and 5 μM) increased p27, both in the cytosol and nucleus. HCB (5 μM) induced a concomitant decrease in nuclear cyclin D1 protein levels, in a time-dependent manner. We have also demonstrated that TGF-β1 Smad signaling is involved in HCB-induced alterations of p27 and cyclin D1 protein levels. On the other hand, ERK1/2 activation is not involved in the alteration of cell cycle regulatory proteins.
Fil: Chiappini, Florencia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Pontillo, Carolina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Álvarez, Laura. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Kleiman, Diana Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
description Hexachlorobenzene (HCB) is an organochlorine pesticide widely distributed in the environment. In this study we have demonstrated that HCB induced loss of cell viability and alterations in cell cycle regulation in FRTL-5 rat thyroid cells. Analysis of cell cycle distribution by flow cytometric analysis demonstrated that HCB induced cell cycle arrest at G2/M and at G0/G1 phase, inhibiting cell cycle progression at the G1/S phase, after 24 h and 72 h of treatment. HCB-treatment resulted in an increase in transforming growth factor-beta (TGF-β1) mRNA levels, a negative regulator of cell growth in thyroid epithelial cells. Time-dependent studies showed that both cytosolic and nuclear p27 protein levels were increased by 5 μM HCB. After 24 h of treatment, total p27 in whole cells lysate was increased. Dose-dependent studies, demonstrated that HCB (0.005, 0.05, 0.5 and 5 μM) increased p27, both in the cytosol and nucleus. HCB (5 μM) induced a concomitant decrease in nuclear cyclin D1 protein levels, in a time-dependent manner. We have also demonstrated that TGF-β1 Smad signaling is involved in HCB-induced alterations of p27 and cyclin D1 protein levels. On the other hand, ERK1/2 activation is not involved in the alteration of cell cycle regulatory proteins.
publishDate 2014
dc.date.none.fl_str_mv 2014-10
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/11336/13812
Chiappini, Florencia Ana; Pontillo, Carolina Andrea; Randi, Andrea Silvana; Álvarez, Laura; Kleiman, Diana Leonor; Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications; Elsevier; Toxicology Letters; 230; 1; 10-2014; 1-9
0378-4274
url http://hdl.handle.net/11336/13812
identifier_str_mv Chiappini, Florencia Ana; Pontillo, Carolina Andrea; Randi, Andrea Silvana; Álvarez, Laura; Kleiman, Diana Leonor; Hexachlorobenzene induces TGF-β1 expression, which is a regulator of p27 and cyclin D1 modifications; Elsevier; Toxicology Letters; 230; 1; 10-2014; 1-9
0378-4274
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0378427414012077
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.toxlet.2014.08.002
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
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 13.070432

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