Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PLC/PRF/5, a tissue culture cell line derived from a human hepatocellular carcinoma and producing hepatitis B surface antigen (HBsAg), was studied by immune and enzyme histochemical techniques. HBsAg was demonstrated in the cytoplasm and on the surface of tumor cells. The percentage of HBsAg-positive cells in subculture increased with time until almost all cells expressed HBsAg when the monolayer reached confluence. Similar patterns were found for alpha 1-anti-trypsin and carcino-embryonic antigen, whereas alpha-fetoprotein was observed only in small foci of cells. Hepatitis B core antigen and albumin were not detected. gamma-Glutamyl transferase activity was markedly increased in the tumor cells, whereas adenosine triphosphatase and glucose-6-phosphatase activities were not demonstrable. Patterns of antigenic expression and enzyme phenotype of PLC/PRF/5 cells show remarkable resemblance to those observed in vivo in human hepatocellular carcinoma. Therefore, this cell line may be a useful model to study the control and modulation of both oncofetal antigens and HBsAg.
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PMID:Immune and enzyme histochemical studies of a human hepatocellular carcinoma cell line producing hepatitis B surface antigen. 616 57

Two mutations, R69D and K115E, converted a bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) to a phosphatase with much higher specific activity toward glucose-6-phosphate than inositol-1-phosphate. PI-PLC single mutations R69D and K115E can cleave PI but lack any demonstrable phosphatase activity. The bacterial PI-PLC has no sequence homology with known glucose-6-phosphatase enzymes, which need His, Arg, and negatively charged residues (Asp or Glu) at the active site. The change in chemical reaction and substrate specificity can be rationalized by energy minimization of the mutant with I-1-P or G-6-P bound.
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PMID:Mutation of two active-site residues converts a phosphatidylinositol-specific phospholipase C to a glucose phosphatase. 1474 54

Fatty acids serve vital functions as sources of energy, building materials for cellular structures, and modulators of physiological responses. Therefore, this study examined the effect of linoleic acid on glucose production and its related signal pathways in primary cultured chicken hepatocytes. Linoleic acid (double-unsaturated, long chain) increased glucose production in a dose (> or =10(-4) M)- and time (> or =8 h)-dependent manner. Both oleic acid (monounsaturated, long chain) and palmitic acid (saturated, long chain) also increased glucose production, whereas caproic acid (saturated, short chain) failed to increase glucose production. Linoleic acid increased G protein-coupled receptor 40 (GPR40; also known as free fatty acid receptor-1) protein expression and glucose production that was blocked by GPR40-specific small interfering RNA. Linoleic acid increased intracellular calcium concentration, which was blocked by EGTA (extracellular calcium chelator)/BAPTA-AM (intracellular calcium chelator), U-73122 (phospholipase C inhibitor), nifedipine, or methoxyverapamil (L-type calcium channel blockers). Linoleic acid increased cytosolic phospholipase A(2) (cPLA(2)) phosphorylation and the release of [(3)H]-labeled arachidonic acid. Moreover, linoleic acid increased the level of cyclooxygenase-2 (COX-2) protein expression, which stimulated the synthesis of prostaglandin E(2) (PGE(2)). The increase in PGE(2) production subsequently stimulated peroxisome proliferator-activated receptor (PPAR) expression, and MK-886 (PPAR-alpha antagonist) and GW-9662 (PPAR-delta antagonist) inhibited glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. In addition, linoleic acid-induced glucose production was blocked by inhibition of extracellular and intracellular calcium, cPLA(2), COX-2, or PPAR pathways. In conclusion, linoleic acid promoted glucose production via Ca(2+)/PLC, cPLA(2)/COX-2, and PPAR pathways through GPR40 in primary cultured chicken hepatocytes.
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PMID:Linoleic acid stimulates gluconeogenesis via Ca2+/PLC, cPLA2, and PPAR pathways through GPR40 in primary cultured chicken hepatocytes. 1884 27

18F-fluorodeoxyglucose (FDG) uptake in hepatocellular carcinoma (HCC) is associated with tumor differentiation and expression of P-glycoprotein (P-gp), a drug efflux pump that plays an important role in chemoresistance. The aim of the study was to clarify the factors that affects FDG uptake in HCC in vivo and in vitro. The standardized uptake value (SUV) and the tumor to non-tumor SUV ratio (TNR) for FDG uptake in HCC in vivo was determined by FDG-PET in 28 patients. Expression levels of glucose transporter-1 (GLUT-1), GLUT-2 and type II hexokinase (HK-II) were examined immunohistochemically in resected specimens. The glucose-6-phosphatase (G-6-Pase) activity was determined in tissue homogenates. In vitro, PLC/PRF/5 cells and doxorubicin-resistant PLC/DOR cells were used to examine the effect of P-gp on FDG uptake. The effects of two P-gp inhibitors, verapamil and cepharanthine, on accumulation of FDG were also examined. in vivo, GLUT-1 expression was low in HCCs, but was significantly higher in poorly differentiated HCCs than in moderately differentiated HCCs (P=0.043) and was positively correlated with SUV (r=0.75, P<0.0001) and TNR (r=0.7, P<0.0001). GLUT-2 and HK-II expression and G-6-Pase activity were not correlated with tumor differentiation, SUV or TNR. P-gp was over-expressed in PLC/DOR cells, and accumulation of FDG was significantly higher in PLC/PRF/5 cells than in PLC/DOR cells (P=0.04). Verapamil and cepharanthine restored FDG uptake in PLC/DOR cells, but not in PLC/PRF/5 cells. Collectively, our results show that FDG uptake in HCC is weakly correlated with GLUT-1 expression, and that FDG could be a substrate of P-gp, which may act as an efflux pump to reduce FDG accumulation.
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PMID:P-glycoprotein expression affects 18F-fluorodeoxyglucose accumulation in hepatocellular carcinoma in vivo and in vitro. 1936 Mar 42