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dc.contributor.author
Abood, S.
dc.contributor.author
Veisaga, M. L.
dc.contributor.author
Lopez, Luis Alberto
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dc.contributor.author
Barbieri, Maria Araceli
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dc.date.available
2019-11-29T20:24:43Z
dc.date.issued
2018-08
dc.identifier.citation
Abood, S.; Veisaga, M. L.; Lopez, Luis Alberto; Barbieri, Maria Araceli; Dehydroleucodine inhibits mitotic clonal expansion during adipogenesis through cell cycle arrest; John Wiley & Sons Ltd; Phytotherapy Research; 32; 8; 8-2018; 1583-1592
dc.identifier.issn
0951-418X
dc.identifier.uri
http://hdl.handle.net/11336/91028
dc.description.abstract
Aberrant levels of preadipocyte differentiation, triggered by adipocyte hyperplasia and hypertrophy, results in the obesogenic phenotype. Obesity is a risk factor for several metabolic disorders. In this paper, dehydroleucodine inhibited the accumulation of lipid droplets and decreased the elevations of triglycerides, and this inhibitory effect occurred during the early stage of adipogenesis. Thus, not only did dehydroleucodine downregulate the expression of C/EBPα and PPARγ, it also strongly blocked the expression of C/EBPβ, an early stage biomarker of early adipogenesis, in a concentration-dependent manner. The proliferation of preadipocytes was dramatically suppressed when dehydroleucodine was added to the medium as early as 24 hr. These results indicate that dehydroleucodine may specifically affect mitotic clonal expansion to inhibit preadipocyte differentiation. Dehydroleucodine arrested the cell cycle at the G0/G1 phase, increased p27 and decreased both cyclins A and D and their partners (e.g., CDK2 and CDK4). Additionally, dehydroleucodine decreased phosphorylation of Erk1/2 and Akt. Furthermore, dehydroleucodine downregulated expression of histone demethylase JMJD2B as well as repressed the expression of histone methyltransferase MLL4, which in turn diminished the expression of C/EBPβ and PPARγ, respectively. Collectively, our results indicate that dehydroleucodine inhibits preadipocyte differentiation by blocking mitotic clonal expansion via cell cycle arrest, which may be mediated by regulation of selective histone methylation/demethylation in transcription activation during the early step of adipogenesis.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
John Wiley & Sons Ltd
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ADIPOGENESIS
dc.subject
C/EBPΑ
dc.subject
C/EBPΒ
dc.subject
MITOTIC CLONAL EXPANSION
dc.subject
PPARΓ
dc.subject
SESQUITERPENE LACTONE
dc.subject.classification
Biología Celular, Microbiología
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Dehydroleucodine inhibits mitotic clonal expansion during adipogenesis through cell cycle arrest
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-21T20:07:21Z
dc.journal.volume
32
dc.journal.number
8
dc.journal.pagination
1583-1592
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Londres
dc.description.fil
Fil: Abood, S.. Florida International University; Estados Unidos
dc.description.fil
Fil: Veisaga, M. L.. Florida International University; Estados Unidos
dc.description.fil
Fil: Lopez, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
dc.description.fil
Fil: Barbieri, Maria Araceli. Fairchild Tropical Botanic Garden; . Florida International University; Estados Unidos
dc.journal.title
Phytotherapy Research
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/ptr.6089
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/ptr.6089
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