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dc.contributor.author
Robert, María Celeste
dc.contributor.author
Furlan, Giulia
dc.contributor.author
Rosso, Natalia
dc.contributor.author
Gambaro, Sabrina Eliana
dc.contributor.author
Apitsionak, Faina
dc.contributor.author
Vianello, Eleonora
dc.contributor.author
Claudio, Tiribelli
dc.contributor.author
Gazzin, Silvia
dc.date.available
2017-07-27T18:03:25Z
dc.date.issued
2013-11
dc.identifier.citation
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
dc.identifier.issn
1932-6203
dc.identifier.uri
http://hdl.handle.net/11336/21477
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Hyperbilirubinemia
dc.subject
Cerebellum
dc.subject
Cell Cycle
dc.subject
Apoptosis
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Alterations in the Cell Cycle in the Cerebellum of Hyperbilirubinemic Gunn Rat: A Possible Link with Apoptosis?
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-07-26T17:20:52Z
dc.journal.volume
8
dc.journal.number
11
dc.journal.pagination
1-13; e79073
dc.journal.pais
Estados Unidos
dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Robert, María Celeste. Centro Studi Fegato; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Furlan, Giulia. Centro Studi Fegato; Italia
dc.description.fil
Fil: Rosso, Natalia. Centro Studi Fegato; Italia
dc.description.fil
Fil: Gambaro, Sabrina Eliana. Centro Studi Fegato; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Apitsionak, Faina. Centro Studi Fegato; Italia
dc.description.fil
Fil: Vianello, Eleonora. Centro Studi Fegato; Italia
dc.description.fil
Fil: Claudio, Tiribelli. Centro Studi Fegato; Italia. Universita Degli Studi Di Trieste; Italia
dc.description.fil
Fil: Gazzin, Silvia. Centro Studi Fegato; Italia
dc.journal.title
Plos One
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0079073
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0079073
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815147/


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