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)

von Hippel Lindau (VHL) disease is a hereditary cancer syndrome caused by biallelic inactivation of the VHL tumor suppressor gene. The most widely known function of VHL is to limit normoxic protein expression of hypoxia-inducible factor-alpha (HIF-alpha). Loss of the functional VHL gene causes constitutive stabilization of HIF-alpha that primarily up-regulates hypoxia-inducible genes even at normal oxygen concentration, which in turn contribute to VHL tumor progression. We report on the novel function of VHL in hepatic glucose storage and disposal. VHL deletion in adult mouse liver quickly leads to increased accumulation of glycogen granules as well as lipid droplets. This abnormal glycogen storage in VHL-inactivated liver arises at least in part from significantly reduced expression of two key liver-specific glucose metabolism genes, glucose transporter-2 (GLUT2) and glucose-6-phosphatase (G-6-Pase). The expression pattern of these genes in VHL knock-out liver was in contrast to that of well-known HIF target genes, such as PGK, Glut-1, VEGF, and EPO, all of which are highly elevated upon VHL inactivation. Our findings suggest that two distinct signaling pathways exist at the downstream of VHL controlling different sets of gene expression. Following VHL inactivation, one pathway causes oxygen-independent overexpression of classic hypoxia-inducible genes and the other one described here suppresses expression of the genes important for liver glucose metabolism.
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PMID:von Hippel Lindau tumor suppressor regulates hepatic glucose metabolism by controlling expression of glucose transporter 2 and glucose 6-phosphatase. 1720 15

The shortage of organ donors has impeded the development of human hepatocyte transplantation. Immortalized hepatocytes could provide an unlimited supply of transplantable cells. To determine whether immortalized hepatocytes could provide global metabolic support in end-stage liver disease, rat hepatocyte clones were developed by transduction with the gene encoding the Simian virus 40 T antigen (SVT) using the human artificial minichromosome (HAC). The SVLT sequence was excised by FRT recombination. Following HAC infusion, the transduced hepatocytes express SVT, blasticidine resistance (BS), and the PGK promoter TK gene. Forty-six cell clones were obtained and at least partially characterized, as previously described, for albumin, alpha-1-antitrypsin, glucose-6-phosphatase (G6Pase), dipeptidylpeptidase 4 (Dpp4), gamma-glutamyltransferase 1 (Ggt), SVT, and beta-actin expression using RT-PCR. Clones were also assessed for albumin secretion into the culture medium using ELISA. All of the cell line secreted approximately 10 mg/dl of albumin, which is equivalent to the amount secreted by primary hepatocytes. In further experiments, this cell line will be used for transplantable cells or artificial organ using HAC. These results represent an important step toward the development of immortalized hepatocytes.
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PMID:Immortalized hepatocytes using human artificial chromosome. 1846 46

n-3 highly unsaturated fatty acids (n-3 HUFAs) have been shown to suppress lipid accumulation and improve protein utilization in grass carp; however, little is known about the underlying molecular mechanism. Hence, we analyzed the hepatopancreas transcriptome of grass carp (Ctenopharyngodon idellus) fed either lard oil (LO) or fish oil (FO) diets. RNA-seq data showed that 125 genes were significantly up-regulated and 107 were significantly down-regulated in the FO group. Among them, 17 lipid metabolism related genes, 12 carbohydrate metabolism related genes, and 34 protein metabolism related genes were selected. Lipid metabolism related genes, such as very long-chain acyl-CoA synthetase (ACSVL),carnitine O-palmitoyltransferase 1 (CPT1) and carnitine-acylcarnitine translocase (CACT), were up-regulated in the FO group. But the genes of diacylglycerol O-acyltransferase 2 (DGAT2) and stearoyl-CoA desaturase (SCD) were down-regulated. Down-regulation of glycolysis related genes, such as 6-phosphofructokinase (PFK), phosphoglycerate kinase (PGK) and pyruvate dehydrogenase kinase (PDK), added with up-regulation of gluconeogenesis related genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), suggests lower utilization of carbohydrate of the FO group. Besides, dietary FO also influenced the protein metabolism related genes, such as up-regulation of genes involved in digestion of dietary protein, mRNA transcription, protein translation and amino acid utilization, down-regulation of genes involved in mRNA degradation and ubiquitination of protein. Interestingly, the up-regulation of mitochondrial uncoupling protein 2 (UCP2) and down-regulation of oxidative phosphorylation related genes (cytochrome c oxidase subunit 4 isoform 2 [COX4I2], HIG1 domain family member 1A [HIGD1A] and cytochrome-b5 reductase [CYB5R]) suggest that energy metabolism may be also influenced by dietary fatty acid composition. These findings presented here provide a comprehensive understanding of the molecular mechanisms governing the effects of fish oil in grass carp.
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PMID:Comparative analysis of the hepatopancreas transcriptome of grass carp (Ctenopharyngodon idellus) fed with lard oil and fish oil diets. 2586