Search results for "Expression"
showing 10 items of 5168 documents
The unique complexity of the CYP3A4 upstream region suggests a nongenetic explanation of its expression variability.
2010
The individually variable and unpredictable expression of CYP3A4 compromises therapies with 50% of contemporary drugs. Gene variants explain only a fraction of this variability.We investigated the evolution of CYP3A4 transcriptional regulation by nuclear receptors such as the xenobiotics sensors PXR and CAR.The combination of a proximal ER6 element with XREM and CLEM represents the original scheme of CYP3A regulation by nuclear receptors in placental mammals. Among human CYP3A genes, this scheme is retained only in CYP3A4, whereas non-CYP3A4 genes lost these elements to a variable extent during primate evolution. In parallel, the number of elements outside XREM and CLEM potentially responsi…
The differentiation of the serotonergic neurons in the Drosophila ventral nerve cord depends on the combined function of the zinc finger proteins Eag…
1997
ABSTRACT The Drosophila ventral nerve cord (vNC) derives from a stereotyped population of neural stem cells, neuroblasts (NBs), each of which gives rise to a characteristic cell lineage. The mechanisms leading to the specification and differentiation of these lineages are largely unknown. Here we analyse mechanisms leading to cell differentiation within the NB 7-3 lineage. Analogous to the grasshopper, NB 7-3 is the progenitor of the Drosophila vNC serotonergic neurons. The zinc finger protein Eagle (Eg) is expressed in NB 7-3 just after delamination and is present in all NB 7-3 progeny until late stage 17. DiI cell lineage tracing and immunocytochemistry reveal that eg is required for norm…
Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety,…
2011
Intensive research is devoted to unravel the neurobiological mechanisms mediating adult hippocampal neurogenesis, its regulation by antidepressants, and its behavioral consequences. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is expressed in the CNS, where its function is unknown. Here, we show, for the first time, the relevance of MIF expression for adult hippocampal neurogenesis. We identify MIF expression in neurogenic cells (in stem cells, cells undergoing proliferation, and in newly proliferated cells undergoing maturation) in the subgranular zone of the rodent dentate gyrus. A causal function for MIF in cell proliferation was shown using genetic (M…
Species-specific mechanisms for cholesterol 7alpha-hydroxylase (CYP7A1) regulation by drugs and bile acids.
2005
The gene encoding cholesterol 7alpha-hydroxylase (CYP7A1) is tightly regulated in order to control intrahepatic cholesterol and bile acid levels. Ligands of the xenobiotic-sensing pregnane X receptor inhibit CYP7A1 expression. To retrace the evolution of the molecular mechanisms underlying CYP7A1 inhibition, we used a chicken hepatoma cell system that retains the ability to be induced by phenobarbital and other drugs. Whereas bile acids regulate CYP7A1 via small heterodimer partner and liver receptor homolog-1, mRNA expression of these nuclear receptors is unchanged by xenobiotics. Instead, drugs repress chicken hepatic nuclear factor 4alpha (HNF4alpha) transcript levels concomitant with a …
SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells
2012
Abstract SAHA, an inhibitor of histone deacetylase activity, has been shown to sensitize tumor cells to apoptosis induced by TRAIL, a member of TNF-family. In this paper we investigated the effect of SAHA/TRAIL combination in two breast cancer cell lines, the ERα−positive MCF-7 and the ERα−negative MDA-MB231. Treatment of MDA-MB231 and MCF-7 cells with SAHA in combination with TRAIL caused detachment of cells followed by anoikis, a form of apoptosis which occurs after cell detachment, while treatment with SAHA or TRAIL alone did not produce these effects. The effects were more evident in MDA-MB231 cells, which were chosen for ascertaining the mechanism of SAHA/TRAIL action. Our results show…
Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells
2010
Historically, our understanding of molecular genetic aspects of human germ cell development has been limited, at least in part due to inaccessibility of early stages of human development to experimentation. However, the derivation of pluripotent stem cells may provide the necessary human genetic system to study germ cell development. In this study, we compared the potential of human induced pluripotent stem cells (iPSCs), derived from adult and fetal somatic cells to form primordial and meiotic germ cells, relative to human embryonic stem cells. We found that ∼5% of human iPSCs differentiated to primordial germ cells (PGCs) following induction with bone morphogenetic proteins. Furthermore, …
Pre- and Post-translational Regulation of Lysyl Oxidase by Transforming Growth Factor-β1 in Osteoblastic MC3T3-E1 Cells
1995
The final enzymatic step required for collagen cross-linking is the extracellular oxidative deamination of peptidyl-lysine and -hydroxylysine residues by lysyl oxidase. A cross-linked collagenous extracellular matrix is required for bone formation. The goals of this study were to compare the transforming growth factor (TGF)-beta 1 regulation of lysyl oxidase enzyme activity and steady state mRNA levels to changes in COL1A1 mRNA levels in MC3T3-E1 osteoblastic cells. TGF-beta 1 increased steady state lysyl oxidase and COL1A1 mRNA levels in a dose- and time-dependent manner. The increase in lysyl oxidase mRNA levels was transient, peaking at 12 h and 8.8 times controls in cells treated with 4…
The yeast putative transcriptional repressor RGM1 is a proline-rich zinc finger protein.
1991
Abstract I have cloned a yeast gene, RGM1, which encodes a proline-rich zinc, finger protein. rgm1 mutants do not show any obvious phenotype but overexpression of RGM1 gene greatly impairs cell growth. The proline-rich region of RGM1 attached to a heterologous DNA binding domain is able to repress the expression of the target gene. RGM1 shares similar zinc finger motifs with the mammalian Egr (early growth response) proteins as well as proline-rich sequences with a high serine and threonine content, suggesting that RGM1 and Egr proteins could have functional similarities.
The polypyrimidine tract-binding protein (PTB) is involved in the post-transcriptional regulation of human inducible nitric oxide synthase expression.
2006
Human inducible nitric oxide synthase (iNOS) expression is regulated by transcriptional and post-transcriptional mechanisms. We have recently shown that the multifunctional RNA-binding proteins KH-type splicing regulatory protein and tristetraprolin are critically involved in the post-transcriptional regulation of human iNOS expression. Several reports have shown that KH-type splicing regulatory protein colocalizes with the polypyrimidine tract-binding protein (PTB), and both RNA-binding proteins seem to interact with the same mRNAs. Therefore we analyzed the involvement of PTB in human iNOS expression. In human DLD-1 cells, cytokine incubation necessary to induce iNOS expression did not ch…
Expression and trafficking of fluorescent viral membrane proteins in baculovirus-transduced BHK cells
2004
Baculovirus vectors show promise as a novel tool for gene delivery into mammalian cells and gene transfer with wild-type baculovirus has been demonstrated both in vitro and in vivo. To study expression and intracellular trafficking of foreign viral membrane proteins in baculovirus-transduced mammalian cells, the envelope proteins, E1 and E2, of rubella virus (RV) were chosen as a model. The enhanced green fluorescent protein (EGFP) and a red fluorescent protein (RFP) were fused to the C-terminus of E1 and E2, respectively. The proteins were cloned under a cytomegalovirus (CMV) promoter and expressed as fluorescent fusion proteins in baculovirus-transduced baby hamster kidney (BHK) cells. Ex…