HAT1
Histone acetyltransferase type B catalytic subunit (EC 2.3.1.48) (Histone acetyltransferase 1) [KAT1]
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The recent evidences indicate that autophagy is associated with a number of pathological processes including cancer, muscular disorder and neurodegeneration in addition to longevity. The efficacy of spermine was investigated on induction of autophagy through histone deacetylation and p53 activation in human fibrosarcoma cell line, HT1080. In this study, it was discovered that spermine increases the activity of HAT and autophagy. It was also identified that the transcriptional activation of p53 and the activation of p21 promoter by spermine are related to the induction of autophagy in reporter gene assay. Furthermore, western blot analyses demonstrated that spermine modulates the expression of proteins related to autophagy and apoptosis. The expression levels of Ac-histone H3, HDAC1, HAT1, p300 and SIRT1 were increased in HT1080 cells treated with spermine. In addition, the expression levels of protein such as acetyl-p53, p-p53, Bcl-2 and caspase-9 inducing apoptosis were increased in the presence of spermine. Moreover, the levels of Mdm2 and caspase-3 expression were reduced in the cells exposed to spermine compared to blank group. These results suggest that activation of HAT in the presence of spermine promotes the induction of autophagy in HT1080 cells through the enhanced activity of p-p53 and acetyl p53.
MeSH Terms
- Acetylation
- Apoptosis
- Autophagy
- Cell Line, Tumor
- Fibrosarcoma
- Gene Expression Regulation, Neoplastic
- Histone Deacetylase 1
- Histones
- Humans
- Longevity
- Spermine
- Tumor Suppressor Protein p53
Keywords
- Acetyl-p53
- Autopagy
- HAT
- SIRT1
- Spermine
Oocyte aging severely decreases the quality of oocytes, which hampers fertilization and subsequent embryo development. In the present study, age-dependent molecular changes in goat oocytes were investigated. First, the quality of goat oocytes with various in vitro culture times (24, 30, 36, 48, and 60 hours) was evaluated on the basis of developmental rates of parthenogenetically activated embryos and apoptosis of cumulus cells (CCs). Second, relative gene expression of six genes (mitochondrial genes: PGC-1α and NRF-1; epigenetic modification genes: SNRPN and HAT1; mitotic spindle checkpoint protein: SMAD2; and hyaluronan synthase gene: HAS3) were analyzed during oocyte aging. Third, we further studied the changes of seven genes (PGC-1α and NRF-1; apoptotic-related genes: BAX and BCL2; hyaluronan synthase gene: HAS2; metabolism-related gene: STAR; and superoxide dismutase gene: SOD1) in CCs during oocyte aging. In these studies, the blastocyst rate gradually decreased and the number of apoptotic cells significantly increased as the culture time increased (P < 0.05). Moreover, relative gene expressions of PGC-1α, NRF-1 and SMAD2 significantly decreased from 24 to 36 hours (P < 0.05), whereas the levels of HAT1 and HAS3 slowly increased as culture was prolonged. Furthermore, the levels of PGC-1α, BCL2, HAS2 and SOD1 quickly reduced, and BAX significantly increased from 24 to 36 hours in aged CCs (P < 0.05). In conclusion, goat oocytes started to age at 30 hours in vitro culture, and gene expression patterns of oocytes and CCs significantly changed as the oocytes aged. Gene expression pattern changes in CCs may provide a convenient and effective way to detect oocyte aging without compromising oocyte integrity.
MeSH Terms
- Aging
- Animals
- Apoptosis
- Cells, Cultured
- Cellular Senescence
- Female
- Gene Expression
- Goats
- Oocytes
- Parthenogenesis
- Time Factors
Keywords
- Aging
- Apoptosis
- Cumulus cells
- Gene expression
- Goat
- Oocytes