Aroclor 1254 Modulates Gene Expression of Nuclear Transcription Factors: Implications for Albumin Gene Transcription and Protein Synthesis in Rat Hepatocyte Cultures

2002 ◽  
Vol 181 (2) ◽  
pp. 79-88 ◽  
Author(s):  
Jürgen Borlak ◽  
Marc Dangers ◽  
Thomas Thum
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Transcription Factors ◽  
Gene Transcription ◽  
Aroclor 1254 ◽  
Rat Hepatocyte ◽  
Hepatocyte Cultures ◽  
Albumin Gene

GATA transcription factors as potentiators of gut endoderm differentiation

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 4909-4917 ◽  
Author(s):  
P. Bossard ◽  
K.S. Zaret
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Site Occupancy ◽  
Gata Factor ◽  
Transcriptional Enhancer ◽  
Gata Factors ◽  
Endoderm Differentiation ◽  
Albumin Gene ◽  
Gut Endoderm

Gene inactivation studies have shown that members of the GATA family of transcription factors are critical for endoderm differentiation in mice, flies and worms, yet how these proteins function in such a conserved developmental context has not been understood. We use in vivo footprinting of mouse embryonic endoderm cells to show that a DNA-binding site for GATA factors is occupied on a liver-specific, transcriptional enhancer of the serum albumin gene. GATA site occupancy occurs in gut endoderm cells at their pluripotent stage: the cells have the potential to initiate tissue development but they have not yet been committed to express albumin or other tissue-specific genes. The GATA-4 isoform accounts for about half of the nuclear GATA-factor-binding activity in the endoderm. GATA site occupancy persists during hepatic development and is necessary for the activity of albumin gene enhancer. Thus, GATA factors in the endoderm are among the first to bind essential regulatory sites in chromatin. Binding occurs prior to activation of gene expression, changes in cell morphology or functional commitment that would indicate differentiation. We suggest that GATA factors at target sites in chromatin may generally help potentiate gene expression and tissue specification in metazoan endoderm development.

Gene Transcription and Translation in Design

2015 ◽  
Author(s):  
Yuemin Hou ◽  
Ji Linhong
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Design Process ◽  
Gene Transcription ◽  
Protein Gene ◽  
Developmental Process ◽  
Transformation Process ◽  
Whole Body ◽  
Engineering Product ◽  
Development Framework

An organism grows from very small to the whole body, while an engineering product is assembled from elements. An organism is formed autonomously and adaptable to his/her/its environment, while an engineering product can only execute very limited actions. The formation of a product determines its functionality. Nature is the best teacher for learning how structures are formed for specific functionality. This paper compares the design process with the developmental process of embryo and proposes a qualitative development framework that simulates the gene transcription and translation in biology. The key step in design is transforming behaviors to structures. This is a process from information to the form and it bears some similarity with the process from DNA to the protein in embryogenesis. Three basic steps are required from DNA to the protein: gene transcription, transport and protein synthesis, which is named as gene expression. Key mechanisms contributing to this transformation process are investigated and a qualitative development framework are constructed for a growth design process. Simple examples are presented for illustration of proposed methods.

scholarly journals The role of insulin-like growth factor 2 receptor-mediated homeobox gene expression in human placental apoptosis, and its implications in idiopathic fetal growth restriction

2019 ◽  
Vol 25 (9) ◽  
pp. 572-585 ◽  
Author(s):  
Lynda K Harris ◽  
Priyadarshini Pantham ◽  
Hannah E J Yong ◽  
Anita Pratt ◽  
Anthony J Borg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Growth Factor ◽  
Cell Growth ◽  
Cell Line ◽  
Gene Transcription ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Homeobox Gene ◽  
Trophoblast Cell

Abstract Fetal growth restriction (FGR) is caused by poor placental development and function early in gestation. It is well known that placentas from women with FGR exhibit reduced cell growth, elevated levels of apoptosis and perturbed expression of the growth factors, cytokines and the homeobox gene family of transcription factors. Previous studies have reported that insulin-like growth factor-2 (IGF2) interacts with its receptor-2 (IGF2R) to regulate villous trophoblast survival and apoptosis. In this study, we hypothesized that human placental IGF2R-mediated homeobox gene expression is altered in FGR and contributes to abnormal trophoblast function. This study was designed to determine the association between IGF2R, homeobox gene expression and cell survival in pregnancies affected by FGR. Third trimester placentas were collected from FGR-affected pregnancies (n = 29) and gestation matched with control pregnancies (n = 30). Functional analyses were then performed in vitro using term placental explants (n = 4) and BeWo trophoblast cells. mRNA expression was determined by real-time PCR, while protein expression was examined by immunoblotting and immunohistochemistry. siRNA transfection was used to silence IGF2R expression in placental explants and the BeWo cell-line. cDNA arrays were used to screen for downstream targets of IGF2R, specifically homeobox gene transcription factors and apoptosis-related genes. Functional effects of silencing IGF2R were then verified by β-hCG ELISA, caspase activity assays and a real-time electrical cell-impedance assay for differentiation, apoptosis and cell growth potential, respectively. IGF2R expression was significantly decreased in placentas from pregnancies complicated by idiopathic FGR (P < 0.05 versus control). siRNA-mediated IGF2R knockdown in term placental explants and the trophoblast cell line BeWo resulted in altered expression of homeobox gene transcription factors, including increased expression of distal-less homeobox gene 5 (DLX5), and decreased expression of H2.0-Like Homeobox 1 (HLX) (P < 0.05 versus control). Knockdown of IGF2R transcription increased the expression and activity of caspase-6 and caspase-8 in placental explants, decreased BeWo proliferation and increased BeWo differentiation (all P < 0.05 compared to respective controls). This is the first study linking IGF2R placental expression with changes in the expression of homeobox genes that control cellular signalling pathways responsible for increased trophoblast cell apoptosis, which is a characteristic feature of FGR.

scholarly journals Ghrelin Increases Neuropeptide Y and Agouti-Related Peptide Gene Expression in the Arcuate Nucleus in Rat Hypothalamic Organotypic Cultures

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5102-5109 ◽  
Author(s):  
Motomitsu Goto ◽  
Hiroshi Arima ◽  
Minemori Watanabe ◽  
Masayuki Hayashi ◽  
Ryouichi Banno ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Neuropeptide Y ◽  
Mrna Expression ◽  
Gene Transcription ◽  
Arcuate Nucleus ◽  
De Novo ◽  
Organotypic Cultures ◽  
Related Peptide ◽  
De Novo Protein Synthesis

Ghrelin, which was identified from the rat stomach, is a potent stimulant for food intake. Several lines of evidence suggest that the orexigenic action of ghrelin is mediated via the neuropeptide Y (NPY) neurons in the arcuate nucleus, although the detailed mechanisms by which ghrelin stimulates NPY neurons are not clear. In this study, we examined the gene regulation of NPY and agouti-related peptide (AGRP), another orexigenic peptide synthesized in the NPY neurons, in the arcuate nucleus by ghrelin in hypothalamic organotypic cultures. Incubation of the hypothalamic explants with ghrelin significantly increased NPY and AGRP mRNA expression in the presence, but not absence, of dexamethasone. Glucocorticoids were also necessary for ghrelin action in vivo because an intracerebroventricular injection of ghrelin significantly increased NPY and AGRP mRNA expression in the arcuate nucleus only in sham-operated, but not in adrenalectomized rats. The stimulatory effects of ghrelin on gene expression were not blocked by a sodium channel blocker tetrodotoxin in the organotypic cultures. Ghrelin also increased NPY heteronuclear (hn) RNA expression, the first transcript that has been used as an indicator for gene transcription. The stimulatory effects of ghrelin on NPY gene expression were abolished in the presence of cycloheximide, which blocks translation, suggesting that de novo protein synthesis is required for ghrelin action. These data suggest that ghrelin stimulates NPY and AGRP gene expression independently of action potentials only in the presence of glucocorticoids. Furthermore, our data demonstrate stimulatory action of ghrelin on NPY gene transcription, which requires de novo protein synthesis.

Transcriptional and posttranscriptional regulation of CSF-1 gene expression in human monocytes

1988 ◽  
Vol 8 (9) ◽  
pp. 3951-3954
Author(s):  
J Horiguchi ◽  
E Sariban ◽  
D Kufe
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Gene Transcription ◽  
Posttranscriptional Regulation ◽  
Drug Exposure ◽  
Actinomycin D ◽  
Protein Synthesis Inhibitor ◽  
Mrna Levels ◽  
Human Monocytes ◽  
Synthesis Inhibitor

Regulation of CSF-1 gene expression was investigated in human monocytes. CSF-1 transcripts were at low or undetectable levels in resting monocytes. However, in monocytes treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), CSF-1 mRNA was increased by 3 h and reached maximal levels by 12 h of drug exposure. When nuclear run-on assays were used, CSF-1 gene transcription was also at low or undetectable levels in resting monocytes but was activated after TPA exposure. TPA-treated monocytes exposed to actinomycin D further demonstrated that the half-life of the CSF-1 mRNA is 0.9 h. The results also demonstrated that the protein synthesis inhibitor, cycloheximide (CHX), increases CSF-1 mRNA levels in both resting and TPA-treated monocytes. These effects of CHX occurred in the absence of detectable increases in CSF-1 gene transcription. Moreover, treatment of monocytes with CHX and actinomycin D demonstrated that inhibition of protein synthesis is associated with stabilization of the CSF-1 transcript. Taken together, these findings indicated that CSF-1 gene expression is controlled at both transcriptional and posttranscriptional levels in human monocytes.

Regulation of Heme Oxygenase-1 Gene Expression by Anoxia and Reoxygenation in Primary Rat Hepatocyte Cultures

2003 ◽  
Vol 228 (5) ◽  
pp. 584-589 ◽  
Author(s):  
Andreas Ohlmann ◽  
Susanne Giffhorn-Katz ◽  
Ivonne Becker ◽  
Norbert Katz ◽  
Stephan Immenschuh
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Protein Synthesis Inhibitor ◽  
Mrna Levels ◽  
Rat Hepatocyte ◽  
Hsp70 Mrna ◽  
Hepatocyte Cultures ◽  
Antioxidant Agents

Heme oxygenase (HO) catalyzes the rate-limiting enzymatic step of heme degradation and regulates the cellular heme content. Gene expression of the inducible isoform of HO, HO-1, is upregulated in response to various oxidative stress stimuli. To investigate the regulatory role of anoxia and reoxygenation (A/R) on hepatic HO-1 gene expression, primary cultures of rat hepatocytes were exposed after an anoxia of 4 hr to normal oxygen tension for various lengths of time. For comparison, gene expression of the noninducible HO isoform, HO-2, and that of the heat-shock protein 70 (HSP70) were determined. During reoxygenation, a marked increase of HO-1 and HSP70 steady-state mRNA levels was observed, whereas no alteration of HO-2 mRNA levels occurred. Corresponding to HO-1 mRNA, an increase of HO-1 protein expression was determined by Western blot analysis. The anoxia-dependent induction of HO-1 was prevented by pretreatment with the transcription inhibitor, actinomycin D, but not by the protein synthesis inhibitor, cycloheximide, suggesting a transcriptional regulatory mechanism. After exposure of hepatocytes to anoxia, the relative levels of oxidized glutathione increased within the first 40 min of reoxygenation. Pretreament of cell cultures with the antioxidant agents, β-carotene and allopurinol, before exposure to A/R led to a marked decrease of HO-1 and HSP70 mRNA expression during reoxygenation. An even more pronounced reduction of mRNA expression was observed after exposure to desferrioxamine. Taken together, the data demonstrate that HO-1 gene expression in rat hepatocyte cultures after A/R is upregulated by a transcriptional mechanism that may be, in part, mediated via the generation of ROS and the glutathione system.

AMP-activated protein kinase regulates gene expression by direct phosphorylation of nuclear proteins

2003 ◽  
Vol 31 (1) ◽  
pp. 224-227 ◽  
Author(s):  
T. Leff
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Protein Kinase ◽  
Gene Transcription ◽  
Metabolic Pathways ◽  
Energy Charge ◽  
Nuclear Proteins ◽  
Cellular Energy ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

One of the primary functions of AMP-activated protein kinase (AMPK) is to regulate the metabolic pathways in response to reduced cellular energy charge. Most of the known targets of the kinase are cytoplasmic enzymes involved in both catabolic and anabolic metabolism. In addition, activation of AMPK in many cells results in changes in the pattern of gene expression. Although some of these effects are undoubtedly secondary responses to modified cellular metabolism, it is possible that in addition to its well-characterized function in the cytoplasm, AMPK also directly phosphorylates and regulates proteins involved in gene transcription. There are now several examples of transcription factors, cofactors and components of the transcriptional core machinery that are directly phosphorylated and regulated by AMPK. Here I review these examples and discuss the significance of AMPK activity in the nucleus.

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