Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?

Autores
Robert, María Celeste; Furlan, Giulia; Rosso, Natalia; Gambaro, Sabrina Eliana; Apitsionak, Faina; Vianello, Eleonora; Claudio, Tiribelli; Gazzin, Silvia
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Severe hyperbilirubinemia causes neurological damage both in humans and rodents. The hyperbilirubinemic Gunn rat shows a marked cerebellar hypoplasia. More recently bilirubin ability to arrest the cell cycle progression in vascular smooth muscle, tumour cells, and, more importantly, cultured neurons has been demonstrated. However, the involvement of cell cycle perturbation in the development of cerebellar hypoplasia was never investigated before. We explored the effect of sustained spontaneous hyperbilirubinemia on cell cycle progression and apoptosis in whole cerebella dissected from 9 day old Gunn rat by Real Time PCR, Western blot and FACS analysis. The cerebellum of the hyperbilirubinemic Gunn rats exhibits an increased cell cycle arrest in the late G0/G1 phase (p < 0.001), characterized by a decrease in the protein expression of cyclin D1 (15%, p < 0.05), cyclin A/A1 (20 and 30%, p < 0.05 and 0.01, respectively) and cyclin dependent kinases2 (25%, p < 0.001). This was associated with a marked increase in the 18 kDa fragment of cyclin E (67%, p < 0.001) which amplifies the apoptotic pathway. In line with this was the increase of the cleaved form of Poly (ADP-ribose) polymerase (54%, p < 0.01) and active Caspase3 (two fold, p < 0.01). These data indicate that the characteristic cerebellar alteration in this developing brain structure of the hyperbilirubinemic Gunn rat may be partly due to cell cycle perturbation and apoptosis related to the high bilirubin concentration in cerebellar tissue mainly affecting granular cells. These two phenomena might be intimately connected.
Fil: Robert, María Celeste. Centro Studi Fegato; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Furlan, Giulia. Centro Studi Fegato; Italia
Fil: Rosso, Natalia. Centro Studi Fegato; Italia
Fil: Gambaro, Sabrina Eliana. Centro Studi Fegato; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Apitsionak, Faina. Centro Studi Fegato; Italia
Fil: Vianello, Eleonora. Centro Studi Fegato; Italia
Fil: Claudio, Tiribelli. Centro Studi Fegato; Italia. Universita Degli Studi Di Trieste; Italia
Fil: Gazzin, Silvia. Centro Studi Fegato; Italia
Materia
HYPERBILIRUBINEMIA
CEREBELLUM
CELL CYCLE
APOPTOSIS
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:11336/21477
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/21477
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?Robert, María CelesteFurlan, GiuliaRosso, NataliaGambaro, Sabrina ElianaApitsionak, FainaVianello, EleonoraClaudio, TiribelliGazzin, SilviaHYPERBILIRUBINEMIACEREBELLUMCELL CYCLEAPOPTOSIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Severe hyperbilirubinemia causes neurological damage both in humans and rodents. The hyperbilirubinemic Gunn rat shows a marked cerebellar hypoplasia. More recently bilirubin ability to arrest the cell cycle progression in vascular smooth muscle, tumour cells, and, more importantly, cultured neurons has been demonstrated. However, the involvement of cell cycle perturbation in the development of cerebellar hypoplasia was never investigated before. We explored the effect of sustained spontaneous hyperbilirubinemia on cell cycle progression and apoptosis in whole cerebella dissected from 9 day old Gunn rat by Real Time PCR, Western blot and FACS analysis. The cerebellum of the hyperbilirubinemic Gunn rats exhibits an increased cell cycle arrest in the late G0/G1 phase (p < 0.001), characterized by a decrease in the protein expression of cyclin D1 (15%, p < 0.05), cyclin A/A1 (20 and 30%, p < 0.05 and 0.01, respectively) and cyclin dependent kinases2 (25%, p < 0.001). This was associated with a marked increase in the 18 kDa fragment of cyclin E (67%, p < 0.001) which amplifies the apoptotic pathway. In line with this was the increase of the cleaved form of Poly (ADP-ribose) polymerase (54%, p < 0.01) and active Caspase3 (two fold, p < 0.01). These data indicate that the characteristic cerebellar alteration in this developing brain structure of the hyperbilirubinemic Gunn rat may be partly due to cell cycle perturbation and apoptosis related to the high bilirubin concentration in cerebellar tissue mainly affecting granular cells. These two phenomena might be intimately connected.Fil: Robert, María Celeste. Centro Studi Fegato; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Furlan, Giulia. Centro Studi Fegato; ItaliaFil: Rosso, Natalia. Centro Studi Fegato; ItaliaFil: Gambaro, Sabrina Eliana. Centro Studi Fegato; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Apitsionak, Faina. Centro Studi Fegato; ItaliaFil: Vianello, Eleonora. Centro Studi Fegato; ItaliaFil: Claudio, Tiribelli. Centro Studi Fegato; Italia. Universita Degli Studi Di Trieste; ItaliaFil: Gazzin, Silvia. Centro Studi Fegato; ItaliaPublic Library of Science2013-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/21477Robert, María Celeste; Furlan, Giulia; Rosso, Natalia; Gambaro, Sabrina Eliana; Apitsionak, Faina; et al.; Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?; Public Library of Science; Plos One; 8; 11; 11-2013; 1-13; e790731932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0079073info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0079073info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815147/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:23:05Zoai:ri.conicet.gov.ar:11336/21477instacron: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 15:23:05.724CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?
title Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?
spellingShingle Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?
Robert, María Celeste
HYPERBILIRUBINEMIA
CEREBELLUM
CELL CYCLE
APOPTOSIS
title_short Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?
title_full Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?
title_fullStr Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?
title_full_unstemmed Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?
title_sort Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?
dc.creator.none.fl_str_mv Robert, María Celeste
Furlan, Giulia
Rosso, Natalia
Gambaro, Sabrina Eliana
Apitsionak, Faina
Vianello, Eleonora
Claudio, Tiribelli
Gazzin, Silvia
author Robert, María Celeste
author_facet Robert, María Celeste
Furlan, Giulia
Rosso, Natalia
Gambaro, Sabrina Eliana
Apitsionak, Faina
Vianello, Eleonora
Claudio, Tiribelli
Gazzin, Silvia
author_role author
author2 Furlan, Giulia
Rosso, Natalia
Gambaro, Sabrina Eliana
Apitsionak, Faina
Vianello, Eleonora
Claudio, Tiribelli
Gazzin, Silvia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HYPERBILIRUBINEMIA
CEREBELLUM
CELL CYCLE
APOPTOSIS
topic HYPERBILIRUBINEMIA
CEREBELLUM
CELL CYCLE
APOPTOSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Severe hyperbilirubinemia causes neurological damage both in humans and rodents. The hyperbilirubinemic Gunn rat shows a marked cerebellar hypoplasia. More recently bilirubin ability to arrest the cell cycle progression in vascular smooth muscle, tumour cells, and, more importantly, cultured neurons has been demonstrated. However, the involvement of cell cycle perturbation in the development of cerebellar hypoplasia was never investigated before. We explored the effect of sustained spontaneous hyperbilirubinemia on cell cycle progression and apoptosis in whole cerebella dissected from 9 day old Gunn rat by Real Time PCR, Western blot and FACS analysis. The cerebellum of the hyperbilirubinemic Gunn rats exhibits an increased cell cycle arrest in the late G0/G1 phase (p < 0.001), characterized by a decrease in the protein expression of cyclin D1 (15%, p < 0.05), cyclin A/A1 (20 and 30%, p < 0.05 and 0.01, respectively) and cyclin dependent kinases2 (25%, p < 0.001). This was associated with a marked increase in the 18 kDa fragment of cyclin E (67%, p < 0.001) which amplifies the apoptotic pathway. In line with this was the increase of the cleaved form of Poly (ADP-ribose) polymerase (54%, p < 0.01) and active Caspase3 (two fold, p < 0.01). These data indicate that the characteristic cerebellar alteration in this developing brain structure of the hyperbilirubinemic Gunn rat may be partly due to cell cycle perturbation and apoptosis related to the high bilirubin concentration in cerebellar tissue mainly affecting granular cells. These two phenomena might be intimately connected.
Fil: Robert, María Celeste. Centro Studi Fegato; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Furlan, Giulia. Centro Studi Fegato; Italia
Fil: Rosso, Natalia. Centro Studi Fegato; Italia
Fil: Gambaro, Sabrina Eliana. Centro Studi Fegato; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Apitsionak, Faina. Centro Studi Fegato; Italia
Fil: Vianello, Eleonora. Centro Studi Fegato; Italia
Fil: Claudio, Tiribelli. Centro Studi Fegato; Italia. Universita Degli Studi Di Trieste; Italia
Fil: Gazzin, Silvia. Centro Studi Fegato; Italia
description Severe hyperbilirubinemia causes neurological damage both in humans and rodents. The hyperbilirubinemic Gunn rat shows a marked cerebellar hypoplasia. More recently bilirubin ability to arrest the cell cycle progression in vascular smooth muscle, tumour cells, and, more importantly, cultured neurons has been demonstrated. However, the involvement of cell cycle perturbation in the development of cerebellar hypoplasia was never investigated before. We explored the effect of sustained spontaneous hyperbilirubinemia on cell cycle progression and apoptosis in whole cerebella dissected from 9 day old Gunn rat by Real Time PCR, Western blot and FACS analysis. The cerebellum of the hyperbilirubinemic Gunn rats exhibits an increased cell cycle arrest in the late G0/G1 phase (p < 0.001), characterized by a decrease in the protein expression of cyclin D1 (15%, p < 0.05), cyclin A/A1 (20 and 30%, p < 0.05 and 0.01, respectively) and cyclin dependent kinases2 (25%, p < 0.001). This was associated with a marked increase in the 18 kDa fragment of cyclin E (67%, p < 0.001) which amplifies the apoptotic pathway. In line with this was the increase of the cleaved form of Poly (ADP-ribose) polymerase (54%, p < 0.01) and active Caspase3 (two fold, p < 0.01). These data indicate that the characteristic cerebellar alteration in this developing brain structure of the hyperbilirubinemic Gunn rat may be partly due to cell cycle perturbation and apoptosis related to the high bilirubin concentration in cerebellar tissue mainly affecting granular cells. These two phenomena might be intimately connected.
publishDate 2013
dc.date.none.fl_str_mv 2013-11
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/11336/21477
Robert, María Celeste; Furlan, Giulia; Rosso, Natalia; Gambaro, Sabrina Eliana; Apitsionak, Faina; et al.; Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?; Public Library of Science; Plos One; 8; 11; 11-2013; 1-13; e79073
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/21477
identifier_str_mv Robert, María Celeste; Furlan, Giulia; Rosso, Natalia; Gambaro, Sabrina Eliana; Apitsionak, Faina; et al.; Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?; Public Library of Science; Plos One; 8; 11; 11-2013; 1-13; e79073
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0079073
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0079073
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815147/
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
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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