Hepatocytes

Certain amino acids, like glutamine and leucine, induce an anabolic response in liver. They activate p70 ribosomal protein S6 kinase (p70S6K) and acetyl-CoA carboxylase (ACC) involved in protein and fatty acids synthesis, respectively. In contrast, the AMP-activated protein kinase (AMPK), which senses the energy state of the cell and becomes activated under metabolic stress, inactivates by phosphorylation key enzymes in biosynthetic pathways thereby conserving ATP.

9p system191 01-06-2013 50 5   Download

Liver metabolism is influenced by hormones and nutrients. Amino acids such as glutamine or leucine induce an anabolic response, which resembles that of insulin in muscle and adipose tissue. In this work, the signalling pathways and the effects of insulin were compared to those of glutamine and leucine in isolated hepatocytes from normal and streptozotocin-diabetic rats.

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The 5¢ flanking region of the bile salt export pump (Bsep) gene was systematically analysed to provide the basis for understanding the mechanisms which regulate Bsep transcription. In addition substrates and drugs were investigated for their ability to alter Bsep promoter activity. Bsep promoter function was restricted to hepatocyte derived HepG2 cells. The 5¢ deletional analysis revealed a biphasic shape of reporter gene activities, indicating a suppressive element between nucleotides )800 and )512. ...

9p research12 01-06-2013 38 4   Download

Glycolysis from [6-3 H]glucose and gluconeogenesis from [U-14 C]glycerol were examined in isolated hepatocytes from fasted rats. A 5 mMbolus of glycerol inhibited phosphory-lationof 40 mMglucoseby50%andglycolysis bymore than 60%, and caused cellular ATP depletion and glycerol 3-phosphate accumulation. Gluconeogenesis from 5 mM glycerol was una€ected by the presence of 40 mMglucose.

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Hepatopoietin (HPO) is a novel human hepatotrophic growth factor. Recently, we demonstrated that the extra-cellular ligand form of HPO can stimulate proliferation of hepatic cells via its specific receptor, which is on the surface of these cells.Also, the intracellular formofHPOpotentiates the transcriptional factor AP-1. Intriguingly, a variety of HPO complexes with different molecular masses were detected in hepatocytes.

6p research12 23-04-2013 25 5   Download

The hepatocyte growth factor-regulated tyrosine kinase substrate Hrs is an early endosomal protein that is thought to play a regulatory role in the trafficking of growth factor/ receptor complexes through early endosomes. Stimulation of cells with epidermal growth factor (EGF) rapidly leads to phosphorylation of Hrs, raising the question whether the receptor tyrosine kinase phosphorylates Hrs directly. Here, we present evidence that a downstream kinase, rather than the active receptor kinase is responsible. ...

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Metabolite channelling, the process in which consecutive enzymes have confined substrate transfer in metabolic pathways, has been proposed as a biochemical mechanism that has evolved because it enhances catalytic rates and protects unstable intermediates. Results from experiments on the synthesis of radioactive urea [Cheung, C., Cohen, N.S. & Raijman, L (1989)J. Biol. Chem.264, 4038–4044] have been interpreted as implying channelling of arginine between argininosuccinate lyase and arginase in permeabi-lized hepatocytes. ...

9p tumor12 20-04-2013 35 1   Download

Liver microsomal preparations are routinely used to predict drug interactions that can occurin vivo as a result of inhi-bition of cytochrome P450 (CYP)-mediated metabolism. However, the concentration of free drug (substrate and inhibitor)at its intrahepatic site of action, a variable that cannot be directly measured, may be significantly different from that in microsomal incubation systems.

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Multiple signalling pathways are involved in themechanism by which insulin stimulates hepatic glycogen synthesis. In this study we used selective inhibitors of glycogen synthase kinase-3 (GSK-3) and an allosteric inhibitor of phosphory-lase (CP-91149) that causes dephosphorylation of phos-phorylasea, to determine the relative contributions of inactivation of GSK-3 and dephosphorylation of phos-phorylaseaas alternative pathways in the stimulation of glycogen synthesis by insulin in hepatocytes.

9p fptmusic 16-04-2013 41 3   Download

Post ischaemic cell calcium invasion has been described as one of the main causes of graft failure. Protective effects of calcium antagonists have been investigated but are not con-vincing and their mechanisms of action remain unclear. In this work we tested the protective effect of a new calcium inhibitor described to block a calcium current insensitive to all known calcium blockers. Specific mapacalcine receptors were first characterized on rat hepatocytesmembranes using the 125 I-labeledmapacalcine....

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In the search for new ligands for the plasminogen kringle 4 binding-protein tetranectin, it has been found by ligand blot analysis andELISAthat tetranectinspecificallybound to the plasminogen-like hepatocyte growth factor and tissue-type plasminogen activator.The dissociation constants of these complexes were found to be within the same order of mag-nitude as the one for the plasminogen-tetranectin complex. The study also revealed that tetranectin did not interact with the kindred proteins: macrophage-stimulating protein, urokinase-type plasminogen activator and prothrombin....

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The therapeutic effect of iron (Fe) chelators on the poten-tially toxic plasma pool of nontransferrin-bound iron (NTBI), often present in Fe overload diseases and in some cancer patients during chemotherapy, is of considerable interest. In the present investigation, several multidentate pyridinones were synthesized and compared with their bidentateanalogue, deferiprone

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Bilitranslocase is a carrier protein localized at the basolateral domain of the hepatocyte plasma membrane. It transports various organic anions, including bromosulfophthalein and anthocyanins. Functional studies in subcellular fractions enriched in plasma membrane revealed a high-affinity binding site for bilirubin, associated with bilitranslocase.

14p fptmusic 12-04-2013 38 3   Download

Diacylglycerol (DAG) andproteinkinase C(PKC) isoforms have been implicated in insulin signalling in muscle and fat cells.We evaluated the involvement ofDAGandPKCin the action of insulin in adult rat hepatocytes culturedwith dexa-methasone, but in the absence of serum, for 48 h. Our results show that although insulin stimulated glycolysis and glycogen synthesis, it had no effect on DAG mass or molecular species composition.

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A bio-nanocapsule (BNC), composed of the surface antigen (sAg) of the hepatitis B virus, is an efficient nanomachine with which to accomplish the liver-specific delivery of genes and drugs. Approximately 110 molecules of sAg are associated to form a BNC particle with an average diameter of 130 nm. TheLprotein is an sAg peptide composed mainly of preS and S regions. The preS region, with specific affinity for human hepatocytes, is localized in the N-terminus.

10p fptmusic 11-04-2013 37 2   Download

Pharmacological activation or overexpression of glucokinase in hepatocytes stimulates glucose phosphorylation, glycolysis and glycogen synthesis. We used an inhibitor of glucose 6-phosphate (Glc6P) hydrolysis, namely the chlorogenic derivative, 1-[2-(4-chloro-phenyl)-cyclopropylmethoxy]-3, 4-di-hydroxy-5-(3-imidazo[4,5-b]pyridin-1-yl-3-phenyl-acryloyloxy)-cyclohexane-

11p dell39 27-03-2013 51 4   Download

Hepatocyte growth factor like⁄macrophage stimulating protein (HGFl⁄MSP) and hepatocyte growth factor⁄scatter factor (HGF⁄SF) define a distinct family of vertebrate-specific growth factors structurally related to the blood proteinase precursor plasminogen and with important roles in development and cancer.

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Mutations in neuroserpin anda1-antitrypsin cause these proteins to form ordered polymers that are retained within the endoplasmic reticulum of neurones and hepatocytes, respectively. The resulting inclusions underlie the dementia familial encephalopathy with neuroserpin inclusion bodies (FENIB) and Z a1-antitrypsin-associated cirrhosis.

13p inspiron33 26-03-2013 49 5   Download

Hepatic insulin resistance in the leptin-receptor defective Zucker fa⁄fa rat is associated with impaired glycogen synthesis and increased activity of phosphorylase-a. We investigated the coupling between phosphorylase-a and glycogen synthesis in hepatocytes from fa⁄fa rats by modulating the concentration of phosphorylase-a.

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Control analysis of the glycolytic flux was carried out in two fast-growth tumor cell types of human and rodent origin (HeLa and AS-30D, respect-ively). Determination of the maximal velocity (Vmax) of the 10 glycolytic enzymes from hexokinase to lactate dehydrogenase revealed that hexokin-ase (153–306 times) and phosphfructokinase-1 (PFK-1) (22–56 times) had higher over-expression in rat AS-30D hepatoma cells than in normal freshly isolated rat hepatocytes.

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