Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.9 (glucose-6-phosphatase)
3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We characterized the effects of calorie restriction (CR) on the expression of key glycolytic, gluconeogenic, and nitrogen-metabolizing enzymes in mice. Of the gluconeogenic enzymes investigated, liver glucose-6-phosphatase mRNA increased 1.7- and 2. 3-fold in young and old CR mice. Phosphoenolpyruvate carboxykinase mRNA and activity increased 2.5- and 1.7-fold in old CR mice. Of the key glycolytic enzymes, pyruvate kinase mRNA and activity decreased approximately 60% in CR mice. Hepatic phosphofructokinase-1 and pyruvate dehydrogenase mRNA decreased 10-20% in CR mice. Of the genes that detoxify ammonia generated from protein catabolism, hepatic glutaminase, carbamyl phosphate synthase I, and tyrosine aminotransferase mRNAs increased 2.4-, 1.8-, and 1.8-fold with CR, respectively. Muscle glutamine synthetase mRNA increased 1.3- and 2. 1-fold in young and old CR mice. Hepatic glutamine synthetase mRNA and activity each decreased 38% in CR mice. These CR-induced changes are consistent with other studies suggesting that CR may decrease enzymatic capacity for glycolysis and increase the enzymatic capacity for hepatic gluconeogenesis and the disposal of byproducts of muscle protein catabolism.
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PMID:Calories and aging alter gene expression for gluconeogenic, glycolytic, and nitrogen-metabolizing enzymes. 1044 32

We investigated the potential of mouse embryonic stem (ES) cells to differentiate into hepatocytes in vitro. Differentiating ES cells expressed endodermal-specific genes, such as alpha-fetoprotein, transthyretin, alpha 1-anti-trypsin and albumin, when cultured without additional growth factors and late differential markers of hepatic development, such as tyrosine aminotransferase (TAT) and glucose-6-phosphatase (G6P), when cultured in the presence of growth factors critical for late embryonic liver development. Further, induction of TAT and G6P expression was induced regardless of expression of the functional SEK1 gene, which is thought to provide a survival signal for hepatocytes during an early stage of liver morphogenesis. The data indicate that the in vitro ES differentiation system has a potential to generate mature hepatocytes. The system has also been found useful in analyzing the role of growth factors and intracellular signaling molecules in hepatic development.
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PMID:Hepatic maturation in differentiating embryonic stem cells in vitro. 1137 55

Insulin regulates the expression of more than 150 genes, indicating that this is a major action of this hormone. At least eight distinct consensus insulin response sequence (IRSs) have been defined through which insulin can regulate gene transcription. These include the serum response element, the activator protein 1 ('AP-1') motif, the Ets motif, the E-box motif and the thyroid transcription factor 2 ('TTF-2') motif. All of these IRSs mediate stimulatory effects of insulin on gene transcription. In contrast, an element with the consensus sequence T(G/A)TTT(T/G)(G/T), which we refer to as the phosphoenolpyruvate carboxykinase (PEPCK)-like motif, mediates the inhibitory effect of insulin on transcription of the genes encoding PEPCK, insulin-like-growth-factor-binding protein 1 (IGFBP-1), tyrosine aminotransferase and the glucose-6-phosphatase (G6Pase) catalytic subunit. The forkhead transcription factor FKHR has recently been shown to bind this PEPCK-like IRS motif and a model has been proposed in which insulin inhibits gene transcription by stimulating the phosphorylation and nuclear export of FKHR. Our results suggest that this model is consistent with the action of insulin on transcription of the gene encoding IGFBP-1 but not that of the G6Pase catalytic subunit. Thus, even though the IRSs in both promoters seem identical, they are functionally distinct. In addition, in the G6Pase catalytic subunit promoter, hepatocyte nuclear factor 1 ('HNF-1'), acts as an accessory factor to enhance the effect of insulin mediated through the IRS.
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PMID:Insulin-regulated gene expression. 1149 27

A novel recombinant molecule, termed IL-6c and consisting of a chimera of interleukin 6 (IL-6) and its soluble receptor is extremely potent in stimulating proliferation of hematopoietic progenitors. We investigated the effect of the IL-6c on the proliferation and differentiation of E14 fetal hepatocytes. IL-6c, in a dose-dependent manner, stimulated proliferation of E14 fetal rat hepatocytes. Adult hepatocyte mitogens together with IL-6c showed no further effect on proliferation. Hematopoietic stem cells mitogens SCF and flt3 ligand (FL) were also mitogenic for fetal hepatocytes, but did not further enhance the effect of IL-6c on cell proliferation. IL-6c decreased expression of fetal markers alpha-fetoprotein (AFP) and gamma-glutamyltranspeptidase, and induced expression of adult enzyme glucose-6-phosphatase (Gluc-6-P) in E14 hepatocytes. On the other hand, IL-6c strongly reduced, in a dose-dependant manner, expression of albumin and tyrosine aminotransferase (TAT). However, when the cells were grown for 3 days with IL-6c, and IL-6c was removed for the next 5 days, expression of albumin and TAT returned to levels found in control cultures. In conclusion, IL-6c stimulated proliferation and affected gene expression in fetal hepatocytes in culture.
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PMID:Chimeric molecule IL-6/soluble IL-6 receptor is a potent mitogen for fetal hepatocytes. 1517 94

We have previously achieved a high level of long-term liver replacement by transplanting freshly isolated embryonic day (ED) 14 rat fetal liver stem/progenitor cells (FLSPCs). However, for most clinical applications, it will be necessary to use cryopreserved cells that can effectively repopulate the host organ. In the present study, we report the growth and gene expression properties in culture of rat FLSPCs cryopreserved for up to 20 months and the ability of cryopreserved FLSPCs to repopulate the normal adult rat liver. After thawing and placement in culture, cryopreserved FLSPCs exhibited a high proliferation rate: 49.7% Ki-67-positive on day 1 and 34.7% Ki-67-positive on day 5. The majority of cells were also positive for both alpha-fetoprotein and cytokeratin-19 (potentially bipotent) on day 5. More than 80% of cultured cells expressed albumin, the asialoglycoprotein receptor, and UDP-glucuronosyltransferase (unique hepatocyte-specific functions). Expression of glucose-6-phosphatase, carbamyl phosphate synthetase 1, hepatocyte nuclear factor 4alpha, tyrosine aminotransferase, and oncostatin M receptor mRNAs was initially negative, but all were expressed on day 5 in culture. After transplantation into the normal adult rat liver, cryopreserved FLSPCs proliferated continuously, regenerated both hepatocytes and bile ducts, and produced up to 15.1% (mean, 12.0% +/- 2.0%) replacement of total liver mass at 6 months after cell transplantation. These results were obtained in a normal liver background under nonselective conditions. This study is the first to show a high level of long-term liver replacement with cryopreserved fetal liver cells, an essential requirement for future clinical applications.
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PMID:Properties of cryopreserved fetal liver stem/progenitor cells that exhibit long-term repopulation of the normal rat liver. 1677 53

Recently it was shown that embryonic stem (ES) cells could differentiate into hepatocytes both in vitro and in vivo, however, prospective hepatic progenitor cells have not yet been isolated and characterized from ES cells. Here we presented a novel 4-step procedure for the differentiation of mouse ES cells into hepatic progenitor cells and then hepatocytes. The differentiated hepatocytes were identified by morphological, biochemical, and functional analyses. The hepatic progenitor cells were isolated from the cultures after the withdrawal of sodium butyrate, which was characterized by scant cytoplasm, ovoid nuclei, the ability of rapid proliferation, expression of a series of hepatic progenitor cell markers, and the potential of differentiation into hepatocytes and bile duct-like cells under the proper conditions that favor hepatocyte and bile epithelial differentiation. The differentiation of hepatocytes from hepatic progenitor cells was characterized by a number of hepatic cell markers including albumin secretion, upregulated transcription of glucose-6-phosphatase and tyrosine aminotransferase, and functional phenotypes such as glycogen storage. The results from our experiments demonstrated that ES cells could differentiate into a novel bipotential hepatic progenitor cell and mature into hepatocytes with typical morphological, phenotypic and functional characteristics, which provides an useful model for the studies of key events during early liver development and a potential source of transplantable cells for cell-replacement therapies.
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PMID:In vitro differentiation of hepatic progenitor cells from mouse embryonic stem cells induced by sodium butyrate. 1688 15

Human embryonic stem cells (hESCs) have enormous potential as a source of cells for cell replacement therapies and as a model for early human development. In this study we examined the differentiating potential of hESCs into hepatocytes in two- and three-dimensional (2D and 3D) culture systems. Embryoid bodies (EBs) were inserted into a collagen scaffold 3D culture system or cultured on collagen-coated dishes and stimulated with exogenous growth factors to induce hepatic histogenesis. Immunofluorescence analysis revealed the expression of albumin (ALB) and cytokeratin-18 (CK-18). The differentiated cells in 2D and 3D culture system displayed several characteristics of hepatocytes, including expression of transthyretin, alpha-1-antitrypsin, cytokeratin 8, 18, 19, tryptophan-2,3-dioxygenase, tyrosine aminotransferase, glucose-6-phosphatase (G6P), cytochrome P450 subunits 7a1 and secretion of alpha-fetoprotein (AFP) and ALB and production of urea. In 3D culture, ALB and G6P were detected earlier and higher levels of urea and AFP were produced, when compared with 2D culture. Electron microscopy of differentiated hESCs showed hepatocyte-like ultrastructure, including glycogon granules, well-developed Golgi apparatuses, rough and smooth endoplasmic reticuli and intercellular canaliculi. The differentiation of hESCs into hepatocyte-like cells within 3D collagen scaffolds containing exogenous growth factors, gives rise to cells displaying morphological features, gene expression patterns and metabolic activities characteristic of hepatocytes and may provide a source of differentiated cells for treatment of liver diseases.
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PMID:Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D culture systems in vitro. 1689 78

We previously reported that the in vitro maturation of CD49f(+)Thy1(-)CD45(-) (CD49f positive) fetal hepatic progenitor cells (HPCs) is supported by Thy1-positive mesenchymal cells derived from the fetal liver. These mesenchymal cell preparations contain two populations, one of a cuboidal shape and the other spindle shaped in morphology. In this study, we determined that the mucin-type transmembrane glycoprotein gp38 could distinguish cuboidal cells from spindle cells by immunocytochemistry. RT-PCR analysis revealed differences between isolated CD49f(+/-)Thy1(+)gp38(+)CD45(-) (gp38 positive) cells and CD49f(+/-)Thy1(+)gp38(-)CD45(-) (gp38 negative) cells, whereas both cells expressed mesenchymal cell markers. The coculture with gp38-positive cells promoted the maturation of CD49f-positive HPCs, which was estimated by positivity for periodic acid-Schiff (PAS) staining, whereas the coculture with gp38-negative cells maintained CD49f-positive HPCs negative for PAS staining. The expression of mature hepatocyte markers, such as tyrosine aminotransferase, tryptophan-2,3-dioxygenase, and glucose-6-phosphatase, were upregulated on HPCs by coculture with gp38-positive cells. Furthermore, transmission electron microscopy revealed the acquisition of mature hepatocyte features by HPCs cocultured with gp38-positive cells. This effect on maturation of HPCs was inhibited by the addition of conditioned medium derived from gp38-negative cells. By contrast, the upregulation of bromodeoxyuridine incorporation by HPCs demonstrated the proliferative effect of coculture with gp38-negative cells. In conclusion, these results suggest that in vitro maturation of HPCs promoted by gp38-positive cells may be opposed by an inhibitory effect of gp38-negative cells, which likely maintain the immature, proliferative state of HPCs.
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PMID:Two populations of Thy1-positive mesenchymal cells regulate in vitro maturation of hepatic progenitor cells. 1699 Apr 47

The MHB-2 cell line, established from a mouse hepatoblastoma (HB), was subjected to the reverse transcriptase-polymerase chain reaction (RT-PCR) for evaluation of gene expression related to cell differentiation. RNAs for c-kit, CD34, thy-1, albumin, cytokeratin (CK) 8, 18 and 19 could be detected, but expression of alpha-fetoprotein, glucose-6-phosphatase, tyrosine aminotransferase and CK7 was not observed. MHB-2 cells were positive for CK8/18 but negative for c-kit, CD34, thy-1 and albumin on protein level. Immunohistochemical staining of the HB in vivo revealed diffusely expressed c-kit. Thy-1-positive HB cells were sparsely observed, but the tumor was negative for CD34 and rarely positive for CK8/18. By in situ hybridization, the HB was positive for CK18 but negative for CK19. Slight expression of albumin, but the lack of immature hepatocytic marker suggested some heterogeneous hepatocyte or an undifferentiated cell from other origin. Furthermore, positive expression of CK19 as well as CK8 and CK18 in culture strongly suggested the differentiation into a biliary lineage or the bidirectional state. In conclusion, the present study indicated the mouse HB to have de-differentiated, bipotent, or biliary-like cell characteristics, and considering the histological difference between HB and biliary tumors, it suggests the mouse HB cells are closely like some sort of hepatic undifferentiated cells.
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PMID:Evaluation of gene expression related to hepatic cell maturation and differentiation in a chemically induced mouse hepatoblastoma cell line. 1763 80

In order to enrich hepatocytes differentiated from embryonic stem cells, we developed a novel medium. Since only hepatocytes have the activity of ornithine transcarbamylase, phenylalanine hydroxylase, galactokinase, and glycerol kinase, we expected that hepatocytes would be enriched in a medium without arginine, tyrosine, glucose, and pyruvate, but supplemented with ornithine, phenylanaline, galactose, and glycerol (hepatocyte-selection medium, HSM). Embryoid bodies were transferred onto dishes coated with gelatin in HSM after 4 days of culture. At 18 days after embryoid body formation, a single type of polygonal cell survived with an enlarged intercellular space and micorvilli. These cells were positive for indocyanine green uptake and for mRNAs of albumin, transthyretin, and alpha-feto protein, but negative for mRNAs of tyrosine aminotransferase, alpha1-antitrypsin, glucose-6-phosphatase, and phosphoenol pyruvate carboxykinase. Since cells in HSM were positive for cytokeratin (CK)8 and CK18 (hepatocyte markers) and for CK19 (a marker of bile duct epithelial cells), we concluded that they were hepatoblasts. They showed weaker expression of CCAAT/enhancer-binding protein (C/EBP)alpha than fetal liver (18.5 days of gestation) and expression of C/EBPbeta at a similar level to that of fetal liver. These data support our conclusion that HSM allows the selection of hepatoblast-like cells.
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PMID:Hepatoblast-like cells enriched from mouse embryonic stem cells in medium without glucose, pyruvate, arginine, and tyrosine. 1847 68


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