scholarly journals Cytoplasmic translocation of nuclear lysine-specific demethylase-1 (LSD1/KDM1A) in human hepatoma cells is induced by its inhibitors

2018 ◽  
Author(s):  
Suemi Yabuta ◽  
Yoshihiro Shidoji
Keyword(s):  
Retinoic Acid ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Histone Lysine ◽  
Lysine Specific Demethylase ◽  
Immunofluorescence Studies ◽  
Weak Activity ◽  
Cytoplasmic Translocation ◽  
First Time ◽  
Farnesoic Acid

ABSTRACTHistone-modifiable lysine-specific demethylase-1 (LSD1/KDM1A) is often upregulated in many cancers, including hepatoma, and is regarded as oncoprotein. We previously reported that the hepatoma-preventive geranylgeranoic acid (GGA) inhibits KDM1A activity at the same IC50as that of the clinically used drug tranylcypromine, a verified inhibitor of KDM1A. Here, we report that these inhibitors induced cytoplasmic translocation of nuclear KDM1A in a human hepatoma-derived cell line. Immunofluorescence studies revealed cytoplasmic localization of KDM1A, 3 h after addition of GGA or tranylcypromine in HuH-7 cells. Geranylgeraniol and all-transretinoic acid were both unable to induce translocation of nuclear KDM1A, whereas farnesoic acid showed the weak activity. Furthermore, GGA did not affect subcellular localization of another histone lysine-specific demethylase, KDM5A. This suggests that the inhibitor-induced translocation of nuclear KDM1A to the cytoplasm is specific for KDM1A. These data demonstrate for the first time that KDM1A inhibitors specifically induce the cytoplasmic translocation of nuclear KDM1A.AbbreviationsATRAall-transretinoic acidCoRESTcorepressor for element 1-silencing transcription factorDICdifferential interference contrastFAfarnesoic acidGGOHgeranylgeraniolGGAgeranylgeranoic acidLSD1/KDM1Alysine-specific demethylase-1pHH3phospho-histone H3(Ser10)TCPtrans-2-phenylcyclopropylamine

scholarly journals Retinoic acid receptor-related orphan receptor (ROR) α4 is the predominant isoform of the nuclear receptor RORα in the liver and is up-regulated by hypoxia in HepG2 human hepatoma cells

2002 ◽  
Vol 364 (2) ◽  
pp. 449-456 ◽  
Author(s):  
Caroline CHAUVET ◽  
Brigitte BOIS-JOYEUX ◽  
Jean-Louis DANAN
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Hepg2 Cells ◽  
Transcriptional Activity ◽  
Cobalt Chloride ◽  
Retinoic Acid Receptor ◽  
Orphan Receptor ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Acid Receptor

The retinoic acid receptor-related orphan receptor α (RORα) is critically involved in many physiological functions in several organs. We find that the main RORα isoform in the mouse liver is the RORα4 isoform, in terms of both mRNA and protein levels, while the RORα1 isoform is less abundant. Because hypoxia is a major feature of liver physiology and pathology, we examined the effect of this stress on Rora gene expression and RORα transcriptional activity. HepG2 human hepatoma cells were cultured for 24h under normoxia (20% O2) or hypoxia (10, 2, and 0.1% O2) and the abundance of the Rora transcripts measured by Northern blot and semi-quantitative RT-PCR. Hypoxic HepG2 cells contained more Rora mRNA than controls. This was also observed in rat hepatocytes in primary culture. Cobalt chloride and desferrioxamine also increased the amount of Rora mRNA in HepG2 cells. It is likely that these treatments increase the amount of the RORα4 protein in HepG2 cells as evidenced by Western blotting in the case of desferrioxamine. Transient transfection experiments indicated that hypoxia, cobalt chloride, and desferrioxamine all stimulate RORα transcriptional activity in HepG2 cells. Hence, we believe that RORα participates in the control of gene transcription in hepatic cells and modulates gene expression in response to hypoxic stress.

scholarly journals Role of retinoic acid in the modulation of benzo(a)pyrene-DNA adducts in human hepatoma cells: Implications for cancer prevention

2010 ◽  
Vol 249 (3) ◽  
pp. 224-230 ◽  
Author(s):  
Guo-Dong Zhou ◽  
Molly Richardson ◽  
Inayat S. Fazili ◽  
Jianbo Wang ◽  
Kirby C. Donnelly ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cancer Prevention ◽  
Dna Adducts ◽  
Hepatoma Cells ◽  
Human Hepatoma ◽  
Human Hepatoma Cells

Retinoic acid enhances susceptibility of human hepatoma cells to NK cell-mediated cytolysis via up-regulation of MICA

2002 ◽  
Vol 36 ◽  
pp. 181-182
Author(s):  
Masahisa Jinushi ◽  
Tetsuo Takehara ◽  
Tomohide Tatsumi ◽  
Tatsuya Kanto ◽  
Takuya Miyagi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Nk Cell ◽  
Hepatoma Cells ◽  
Human Hepatoma ◽  
Human Hepatoma Cells

scholarly journals Control of Gene Expression by the Retinoic Acid-Related Orphan Receptor Alpha in HepG2 Human Hepatoma Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (7) ◽  
pp. e22545 ◽  
Author(s):  
Caroline Chauvet ◽  
Amandine Vanhoutteghem ◽  
Christian Duhem ◽  
Gaëlle Saint-Auret ◽  
Brigitte Bois-Joyeux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Hepatoma Cells ◽  
Orphan Receptor ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Control Of Gene Expression ◽  
Receptor Alpha
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