Regulation of cellular processes by PPARγ ligands in neuroblastoma cells is modulated by the level of retinoblastoma protein expression

2004 ◽  
Vol 32 (5) ◽  
pp. 840-842 ◽  
Author(s):  
V.C. Emmans ◽  
H.A. Rodway ◽  
A.N. Hunt ◽  
K.A. Lillycrop
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Trichostatin A ◽  
Neuroblastoma Cells ◽  
Retinoblastoma Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cellular Processes ◽  
Deacetylase Inhibitor

Neuroblastoma is a childhood cancer, which spontaneously regresses. This has led to a search for agents that mimic this process. We show that both natural and synthetic ligands of PPARγ (peroxisome-proliferator-activated receptor γ) inhibit the growth of neuroblastoma cells in vitro. The degree of PPAR activation was attenuated however in the presence of the retinoblastoma protein. Addition of trichostatin A, a histone deacetylase inhibitor, abolished retinoblastoma protein repression of PPAR activity. Moreover, enhanced growth inhibition was observed when neuroblastoma cells were treated with a PPARγ ligand and a histone deacetylase inhibitor, suggesting a combination therapy to treat neuroblastoma might prove more effective than using either agent alone.

scholarly journals Suppression of Adiponectin Gene Expression by Histone Deacetylase Inhibitor Valproic Acid

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 865-874 ◽  
Author(s):  
Liping Qiao ◽  
Jerome Schaack ◽  
Jianhua Shao
Keyword(s):  
Gene Expression ◽  
Valproic Acid ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Adiponectin Gene ◽  
Peroxisome Proliferator Activated Receptor ◽  
Deacetylase Inhibitor

Valproic acid (VPA) has been used for the treatment of epilepsy and bipolar disorders for more than 30 yr. Obesity and insulin resistance are common side effects of VPA treatment. Adiponectin is an adipocyte-derived protein that plays an important role in controlling insulin sensitivity and glucose homeostasis. In this report, we examined the effects of VPA on adiponectin gene expression in C57BL/6J mice and in differentiated 3T3-L1 adipocytes. VPA treatment significantly decreased adiponectin protein and mRNA levels in both mice and 3T3-L1 adipocytes. The adipocyte study showed that VPA inhibited adiponectin gene expression in a dose- and time-dependent manner. Repression of adiponectin expression by VPA occurred at the transcription level and correlated with inhibition of histone deacetylase activity. Therapeutic concentrations of VPA increased overall histone acetylation and increased adiponectin promoter-driven luciferase expression in fibroblasts, but decreased adiponectin promoter activity in differentiated 3T3-L1 adipocytes. VPA treatment decreased adipogenic transcription factor CCAAT/enhancer binding protein-α (C/EBPα) levels and binding of C/EBPα to the adiponectin promoter without altering the levels of peroxisome proliferator-activated receptor-γ and steroid regulatory element binding protein-1. Furthermore, VPA did not suppress adiponectin gene expression in C/EBPα gene-deficient adipocytes that stably expressed exogenous peroxisome proliferator-activated receptor-γ2. Together, these results demonstrate that histone deacetylase inhibitor VPA suppresses adiponectin gene expression in mature adipocytes. The study also provides evidence that diminished C/EBPα protein level and decreased binding at the adiponectin promoter mediate the inhibitory effects of VPA on adiponectin gene transcription.

scholarly journals The Histone Deacetylase Inhibitor Trichostatin A Has Genotoxic Effects in Human Lymphoblasts In Vitro

2006 ◽  
Vol 93 (2) ◽  
pp. 341-347 ◽  
Author(s):  
Andrew J. Olaharski ◽  
Zhiying Ji ◽  
Ji-Young Woo ◽  
Sophia Lim ◽  
Alan E. Hubbard ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Trichostatin A ◽  
Genotoxic Effects ◽  
Deacetylase Inhibitor ◽  
Histone Deacetylase Inhibitor Trichostatin

scholarly journals Effects of Trichostatin A, a Histone Deacetylase Inhibitor, on Mouse Gonadal Development In Vitro

2004 ◽  
Vol 50 (2) ◽  
pp. 227-235 ◽  
Author(s):  
Takuo MIZUKAMI ◽  
Masahiko FUJISAWA ◽  
Yoshiakira KANAI ◽  
Masamichi KUROHMARU ◽  
Yoshihiro HAYASHI
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Trichostatin A ◽  
Gonadal Development ◽  
Deacetylase Inhibitor ◽  
Development In Vitro

scholarly journals Supplementation with the histone deacetylase inhibitor trichostatin A during in vitro culture of bovine embryos

Zygote ◽  
2011 ◽  
Vol 21 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Clara Slade Oliveira ◽  
Naiara Zoccal Saraiva ◽  
Marcela Maria de Souza ◽  
Tatiane de Almeida Drummond Tetzner ◽  
Marina Ragagnin de Lima ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Embryo Quality ◽  
Trichostatin A ◽  
Total Cell ◽  
Background Information ◽  
Bovine Embryos ◽  
Deacetylase Inhibitor ◽  
Blastocyst Hatching

SummaryTrichostatin A (TSA) is a histone deacetylase inhibitor that induces histone hyperacetylation and increases gene expression levels. The aim of the present study was to establish a suitable condition for the use of TSA in in vitro cultures of bovine embryos, and to determine whether TSA would increase blastocyst rates by improvement of chromatin remodelling during embryonic genome activation and by increasing the expression of crucial genes during early development. To test this hypothesis, 8-cell embryos were exposed to four concentrations of TSA for different periods of time to establish adequate protocols. In a second experiment, three experimental groups were selected for the evaluation of embryo quality based on the following parameters: apoptosis, total cell number and blastocyst hatching. TSA promoted embryonic arrest and degeneration at concentrations of 15, 25 and 50 nM. All treated groups presented lower blastocyst rates. Exposure of embryos to 5 nM for 144 h and to 15 nM for 48 h decreased blastocyst hatching. However, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay (TUNEL) assay revealed similar apoptosis rates and total cell numbers in all groups studied. Although, in the present study, TSA treatment did not improve the parameters studied, the results provided background information on TSA supplementation during in vitro culture of bovine embryos and showed that embryo quality was apparently not affected, despite a decrease in blastocyst rate after exposure to TSA.

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