scholarly journals Different statins produce highly divergent changes in gene expression profiles of human hepatoma cells: a pilot study.

2011 ◽  
Vol 58 (4) ◽  
Author(s):  
Agata Leszczynska ◽  
Monika Gora ◽  
Danuta Plochocka ◽  
Grazyna Hoser ◽  
Anna Szkopinska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Statin Therapy ◽  
Hepg2 Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
High Dose ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Key Enzyme ◽  
Coa Reductase

Statins are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the sterol biosynthesis pathway. Statin therapy is commonly regarded as well tolerated. However, serious adverse effects have also been reported, especially during high-dose statin therapy. The aim of our study was to investigate the effect of statins on gene expression profiles in human hepatoma HepG2 cells using Affymetrix Human Genome U133 Plus 2.0 arrays. Expression of 102, 857 and 1091 genes was changed substantially in HepG2 cells treated with simvastatin, fluvastatin and atorvastatin, respectively. Pathway and gene ontology analysis showed that many of the genes with changed expression levels were involved in a broad range of metabolic processes. The presented data clearly indicate substantial differences between the tested statins.

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.

Relationship Between San-Huang-Xie-Xin-Tang and Its Herbal Components on the Gene Expression Profiles in HepG2 Cells

2008 ◽  
Vol 36 (04) ◽  
pp. 783-797 ◽  
Author(s):  
Wen-Yu Cheng ◽  
Shih-Lu Wu ◽  
Chien-Yun Hsiang ◽  
Chia-Cheng Li ◽  
Tung-Yuan Lai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepg2 Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
Major Effect ◽  
Gene Set Enrichment Analysis ◽  
P53 Signaling ◽  
The Relationship ◽  
Herbal Components

Traditional Chinese medicine (TCM) has been used for thousands of years. Most Chinese herbal formulae consist of several herbal components and have been used to treat various diseases. However, the mechanisms of most formulae and the relationship between formulae and their components remain to be elucidated. Here we analyzed the putative mechanism of San-Huang-Xie-Xin-Tang (SHXXT) and defined the relationship between SHXXT and its herbal components by microarray technique. HepG2 cells were treated with SHXXT or its components and the gene expression profiles were analyzed by DNA microarray. Gene set enrichment analysis indicated that SHXXT and its components displayed a unique anti-proliferation pattern via p53 signaling, p53 activated, and DNA damage signaling pathways in HepG2 cells. Network analysis showed that most genes were regulated by one molecule, p53. In addition, hierarchical clustering analysis showed that Rhizoma Coptis shared a similar gene expression profile with SHXXT. These findings may explain why Rhizoma Coptis is the principle herb that exerts the major effect in the herbal formula, SHXXT. Moreover, this is the first report to reveal the relationship between formulae and their herbal components in TCM by microarray and bioinformatics tools.

scholarly journals Proteasome Inhibitors Interrupt the Activation of Non-Canonical NF-κB Signaling Pathway and Induce Cell Apoptosis in Cytarabine-Resistant HL60 Cells

2021 ◽  
Vol 23 (1) ◽  
pp. 361
Author(s):  
Shuo-Yu Wang ◽  
Yin-Hwa Shih ◽  
Tzong-Ming Shieh ◽  
Yu-Hsin Tseng
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Proteasome Inhibitors ◽  
Gene Expression Profiles ◽  
Nuclear Factor Κb ◽  
High Dose ◽  
Hl60 Cells ◽  
Expression Arrays ◽  
Study Results

Over half of older patients with acute myeloid leukemia (AML) do not respond to cytotoxic chemotherapy, and most responders relapse because of drug resistance. Cytarabine is the main drug used for the treatment of AML. Intensive treatment with high-dose cytarabine can increase the overall survival rate and reduce the relapse rate, but it also increases the likelihood of drug-related side effects. To optimize cytarabine treatment, understanding the mechanism underlying cytarabine resistance in leukemia is necessary. In this study, the gene expression profiles of parental HL60 cells and cytarabine-resistant HL60 (R-HL60) cells were compared through gene expression arrays. Then, the differential gene expression between parental HL60 and R-HL60 cells was measured using KEGG software. The expression of numerous genes associated with the nuclear factor κB (NF-κB) signaling pathway changed during the development of cytarabine resistance. Proteasome inhibitors inhibited the activity of non-canonical NF-κB signaling pathway and induced the apoptosis of R-HL60 cells. The study results support the application and possible mechanism of proteasome inhibitors in patients with relapsed or refractory leukemia.

scholarly journals Tissue-specific estrogenic and non-estrogenic effects of a xenoestrogen, nonylphenol

2004 ◽  
Vol 33 (1) ◽  
pp. 243-252 ◽  
Author(s):  
H Watanabe ◽  
A Suzuki ◽  
M Goto ◽  
DB Lubahn ◽  
H Handa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Estrogenic Activity ◽  
Expression Profiles ◽  
Endocrine System ◽  
Gene Expression Profiles ◽  
Binding Activity ◽  
High Dose ◽  
Tissue Specific ◽  
Liver Gene

Alkylphenols perturb the endocrine system and are considered to have weak estrogenic activities. Although it is known that nonylphenol can bind weakly to the estrogen receptor, it is unclear whether all reported effects of nonylphenol are attributable to its estrogen receptor-binding activity. In order to examine whether alkylphenols have similar effects to the natural hormone, estradiol, we used a mouse model to examine the effects of nonylphenol on gene expression and compared it with estradiol. DNA microarray analysis revealed that, in the uterus, most of the genes activated by this alkylphenol at a high dose (50 mg/kg) were also activated by estradiol. At lower doses, nonylphenol (0.5 mg/kg and 5 mg/kg) had little effect on the genes that were activated by estradiol. Thus, we concluded that the effects of nonylphenol at a high dose (50 mg/kg) were very similar to estradiol in uterine tissue. Moreover, since evaluation of estrogenic activity by gene expression levels was comparable with the uterotrophic assay, it indicated that analysis of gene expression profiles can predict the estrogenic activities of chemicals. In contrast to the similar effects of nonylphenol and estradiol observed in the uterus, in the liver, gene expression was more markedly affected by nonylphenol than by estradiol. This indicated that, in the liver, nonylphenol could activate another set of genes that are distinct from estrogen-responsive genes. These results indicated that nonylphenol has very similar effects to estradiol on gene expression in uterine but not in liver tissue, indicating that tissue-specific effects should be considered in order to elucidate the distinct effects of alkylphenols.

Microarray analysis reveals pivotal divergent mRNA expression profiles early in the development of either compensated ventricular hypertrophy or heart failure

2005 ◽  
Vol 21 (3) ◽  
pp. 314-323 ◽  
Author(s):  
Henk P. J. Buermans ◽  
Everaldo M. Redout ◽  
Anja E. Schiel ◽  
René J. P. Musters ◽  
Marian Zuidwijk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Contractile Function ◽  
Pyrrolizidine Alkaloid ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Pressure Overload ◽  
High Dose ◽  
Specific Expression

Myocardial right ventricular (RV) hypertrophy due to pulmonary hypertension is aimed at normalizing ventricular wall stress. Depending on the degree of pressure overload, RV hypertrophy may progress to a state of impaired contractile function and heart failure, but this cannot be discerned during the early stages of ventricular remodeling. We tested whether critical differences in gene expression profiles exist between ventricles before the ultimate development of either a compensated or decompensated hypertrophic phenotype. Both phenotypes were selectively induced in Wistar rats by a single subcutaneous injection of either a low or a high dose of the pyrrolizidine alkaloid monocrotaline (MCT). Spotted oligonucleotide microarrays were used to investigate pressure-dependent cardiac gene expression profiles at 2 wk after the MCT injections, between control rats and rats that would ultimately develop either compensated or decompensated hypertrophy. Clustering of significantly regulated genes revealed specific expression profiles for each group, although the degree of hypertrophy was still similar in both. The ventricles destined to progress to failure showed activation of pro-apoptotic pathways, particularly related to mitochondria, whereas the group developing compensated hypertrophy showed blocked pro-death effector signaling via p38-MAPK, through upregulation of MAPK phosphatase-1. In summary, we show that, already at an early time point, pivotal differences in gene expression exist between ventricles that will ultimately develop either a compensated or a decompensated phenotype, depending on the degree of pressure overload. These data reveal genes that may provide markers for the early prediction of clinical outcome as well as potential targets for early intervention.

scholarly journals Comparison of gene expression profiles of HepG2 cells exposed to Crambescins C1 and A1

2014 ◽  
Vol 1 ◽  
Author(s):  
Sánchez María ◽  
Rubiolo Juan ◽  
Ternon Eva ◽  
Thomas Olivier ◽  
Vega Félix ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepg2 Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles
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