Gamma-tocotrienol modulation of senescence-associated gene expression prevents cellular aging in human diploid fibroblasts
Clinics
; Clinics;67(2): 135-143, 2012. ilus, graf, tab
Article
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| LILACS
| ID: lil-614637
Bibliothèque responsable:
BR1.1
ABSTRACT
OBJECTIVE:
Human diploid fibroblasts undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular aging. The beneficial effects of vitamin E in aging have been established, but studies to determine the mechanisms of these effects are ongoing. This study determined the molecular mechanism of γ-tocotrienol, a vitamin E homolog, in the prevention of cellular aging in human diploid fibroblasts using the expression of senescence-associated genes.METHODS:
Primary cultures of young, pre-senescent, and senescent fibroblast cells were incubated with γ-tocotrienol for 24 h. The expression levels of ELN, COL1A1, MMP1, CCND1, RB1, and IL6 genes were determined using the quantitative real-time polymerase chain reaction. Cell cycle profiles were determined using a FACSCalibur Flow Cytometer.RESULTS:
The cell cycle was arrested in the G0/G1 phase, and the percentage of cells in S phase decreased with senescence. CCND1, RB1, MMP1, and IL6 were upregulated in senescent fibroblasts. A similar upregulation was not observed in young cells. Incubation with γ-tocotrienol decreased CCND1 and RB1 expression in senescent fibroblasts, decreased cell populations in the G0/G1 phase and increased cell populations in the G2/M phase. γ-Tocotrienol treatment also upregulated ELN and COL1A1 and downregulated MMP1 and IL6 expression in young and senescent fibroblasts.CONCLUSION:
γ-Tocotrienol prevented cellular aging in human diploid fibroblasts, which was indicated by the modulation of the cell cycle profile and senescence-associated gene expression.Mots clés
Texte intégral:
1
Indice:
LILACS
Sujet Principal:
Vitamine E
/
Cycle cellulaire
/
Chromanes
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Vieillissement de la cellule
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Beta-Galactosidase
/
Fibroblastes
/
Antioxydants
Type d'étude:
Risk_factors_studies
Limites du sujet:
Humans
langue:
En
Texte intégral:
Clinics
Thème du journal:
MEDICINA
Année:
2012
Type:
Article