scholarly journals Thyromimetic effect of peroxisomal proliferators in rat liver

1991 ◽  
Vol 274 (3) ◽  
pp. 745-751 ◽  
Author(s):  
R Hertz ◽  
R Aurbach ◽  
T Hashimoto ◽  
J Bar-Tana
Keyword(s):  
Thyroid Hormone ◽  
Rat Liver ◽  
Transcriptional Activation ◽  
Rat Hepatocytes ◽  
Nuclear Extract ◽  
Pituitary Cells ◽  
Glycerophosphate Dehydrogenase ◽  
Free Media ◽  
Glucose 6 Phosphate Dehydrogenase

Amphipathic carboxylates, of varying hydrophobic backbones, which act as peroxisomal proliferators (aryloxyalkanoic acids, methyl-substituted dicarboxylic acid) induce in euthyroid or thyroidectomized rats, as well as in rat hepatocytes cultured in 3,5,3′-tri-iodo-L-thyronine (T3)-free media, liver enzyme activities that are classically considered to be thyroid-hormone-dependent (malic enzyme, mitochondrial alpha-glycerophosphate dehydrogenase, glucose-6-phosphate dehydrogenase and S14). The dose required in vivo for the thyromimetic effect of peroxisomal proliferators was 10(3)-fold higher than the dose of T3 required. Similarly, peroxisomal proliferators were active in culture in the range 1-100 microM compared with 1 nM for T3. Their maximal inductive capacities were, however, similar to or greater than that of T3. The thyromimetic effect of peroxisomal proliferators was only partially correlated with their capacities as inducers of liver peroxisomal enzymes. The thyromimetic effect with respect to liver malate dehydrogenase and S14 resulted from an increase in their mRNA contents. The increase in liver S14 mRNA was accounted for by transcriptional activation of the S14 gene. T3 binding to isolated liver nuclei or nuclear extract was competitively displaced by some but not all of the non-thyroidal inducers of the above liver activities. In contrast with the thyromimetic effect induced in liver cells, no increase in growth hormone mRNA was observed in cultured GH1 pituitary cells incubated in the presence of non-thyroidal amphipathic carboxylates. The characteristics of the thyromimetic effect of amphipathic carboxylic peroxisomal proliferators indicate that these agents may act as transcriptional activators of thyroid-hormone-dependent genes in the rat liver.

scholarly journals Regulation of glucose-6-phosphate dehydrogenase synthesis and mRNA abundance in cultured rat hepatocytes

1991 ◽  
Vol 276 (1) ◽  
pp. 245-250 ◽  
Author(s):  
P Manos ◽  
R Nakayama ◽  
D Holten
Keyword(s):  
Energy Source ◽  
Amino Acids ◽  
Rat Hepatocytes ◽  
Fold Increase ◽  
G6pd Activity ◽  
Primary Hepatocytes ◽  
Cultured Rat Hepatocytes ◽  
Free Media ◽  
Glucose 6 Phosphate Dehydrogenase

Conditions were identified which, for the first time, demonstrate that primary hepatocytes can express the same range of glucose-6-phosphate dehydrogenase (G6PD) synthesis and mRNA as in live rats. Primary hepatocytes were cultured without prior exposure to serum, hormones or carbohydrates. Five modulators implicated in G6PD induction in vivo were examined: insulin, dexamethasone, tri-iodothyronine (T3), glucose and fructose, T3 did not affect G6PD activity, and did not interact with carbohydrate to affect the activity of G6PD. Neither glucose nor fructose alone affected G6PD activity, and they did not interact with insulin to increase G6PD activity. Hepatocytes isolated from fasted rats and cultured in serum-free media with amino acids ad the only energy source how a 12-fold increase in G6PD synthesis and mRNA (measured by a solution-hybridization assay). This induction does not require added hormones or carbohydrate. The addition of insulin alone caused another increase in G6PD synthesis and mRNA. There are at least three distinct phases to G6PD induction under these conditions. The largest increase in G6PD synthesis (12-fold) occurs in the absence of any hormones and with amino acids as the only energy source. This phase is due to increased G6PD mRNA. Insulin causes an additional 2-3-fold increase in G6PD synthesis and mRNA. However, dexamethasone and insulin are both required before G6PD synthesis is equal to that in rats which are fasted and refed on a high-carbohydrate diet.

scholarly journals Molecular immunocytochemistry of the CuZn superoxide dismutase in rat hepatocytes.

1988 ◽  
Vol 107 (6) ◽  
pp. 2169-2179 ◽  
Author(s):  
L Y Chang ◽  
J W Slot ◽  
H J Geuze ◽  
J D Crapo
Keyword(s):  
Superoxide Dismutase ◽  
Rat Liver ◽  
Oxidant Stress ◽  
Rat Hepatocytes ◽  
Reaction Rates ◽  
Cytoplasmic Matrix ◽  
Cytosolic Proteins ◽  
Cuzn Superoxide Dismutase ◽  
O2 Production

The distribution of CuZn superoxide dismutase (SOD) molecules in subcellular organelles in rat liver hepatocytes was studied using integrated biochemical, stereological, and quantitative immunocytochemical techniques. A known concentration of purified CuZn SOD in 10% gelatin was embedded alongside the liver tissue for the calculation of CuZn SOD concentrations in hepatocyte organelles and total CuZn SOD in the rat liver. Most of the CuZn SOD was located in the cytoplasmic matrix (73.1%) and in the nucleus (11.9%) with concentrations of 1.36 and 0.71 mg/cm3, respectively. Lysosomes contained the highest concentration (5.81 mg/cm3). Only low concentrations were measured in mitochondria (0.21 mg/cm3). Membrane-bound spaces of rough endoplasmic reticulum (ER), smooth ER, and the Golgi system did not contain significant concentrations of the enzyme. By adding up the concentrations in all subcellular compartments, a total liver content of CuZn SOD was established from the immunocytochemical measurements (0.386 +/- 0.028 mg/gm liver) that agreed closely with those obtained by biochemical assays (0.380 +/- 0.058 mg/gm liver). The average distances between two CuZn SOD molecules can be calculated from enzyme concentrations. It was determined that CuZn SOD molecules in the cytoplasmic matrix and nucleus were 34 and 42 nm apart, respectively. In peroxisomes and mitochondria, average intermolecular distance increased to approximately 60 nm and increased to 136 nm in smooth ER. CuZn SOD is a relatively abundant protein in the cytosol of hepatocytes and its distribution overlaps with major sites of O2- production. The efficiency of protection CuZn SOD can provide to cytosolic proteins from attacks by superoxide anion depends on the rate of O2- production, distribution of CuZn SOD relative to cytosolic proteins, and the relative reaction rates between O2- with both cytosolic proteins and CuZn SOD. Future studies of these substrate-enzyme relationships in vivo can lead to a greater understanding of how cells handle oxidant stress.

scholarly journals Biosynthesis and processing of ribophorins in the endoplasmic reticulum.

1984 ◽  
Vol 99 (3) ◽  
pp. 1076-1082 ◽  
Author(s):  
M G Rosenfeld ◽  
E E Marcantonio ◽  
J Hakimi ◽  
V M Ort ◽  
P H Atkinson ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Posttranslational Modifications ◽  
Rat Hepatocytes ◽  
Direct Analysis ◽  
In Vitro Translation ◽  
Endoplasmic Reticulum Membrane ◽  
Pituitary Cells ◽  
Amino Terminal

Ribophorins are two transmembrane glycoproteins characteristic of the rough endoplasmic reticulum, which are thought to be involved in the binding of ribosomes. Their biosynthesis was studied in vivo using lines of cultured rat hepatocytes (clone 9) and pituitary cells (GH 3.1) and in cell-free synthesis experiments. In vitro translation of mRNA extracted from free and bound polysomes of clone 9 cells demonstrated that ribophorins are made exclusively on bound polysomes. The primary translation products of ribophorin messengers obtained from cultured hepatocytes or from regenerating livers co-migrated with the respective mature proteins, but had slightly higher apparent molecular weights (2,000) than the unglycosylated forms immunoprecipitated from cells treated with tunicamycin. This indicates that ribophorins, in contrast to all other endoplasmic reticulum membrane proteins previously studied, contain transient amino-terminal insertion signals which are removed co-translationally. Kinetic and pulse-chase experiments with [35S]methionine and [3H]mannose demonstrated that ribophorins are not subjected to electrophoretically detectable posttranslational modifications, such as proteolytic cleavage or trimming and terminal glycosylation of oligosaccharide side chain(s). Direct analysis of the oligosaccharides of ribophorin l showed that they do not contain the terminal sugars characteristic of complex oligosaccharides and that they range in composition from Man8GlcNAc to Man5GlcNAc. These findings, as well as the observation that the mature proteins are sensitive to endoglycosidase H and insensitive to endoglycosidase D, are consistent with the notion that the biosynthetic pathway of the ribophorins does not require a stage of passage through the Golgi apparatus.

Comparison of hepatocarcinogen-induced gene expression profiles in conventional primary rat hepatocytes with in vivo rat liver

2012 ◽  
Vol 86 (9) ◽  
pp. 1399-1411 ◽  
Author(s):  
Tatyana Y. Doktorova ◽  
Heidrun Ellinger-Ziegelbauer ◽  
Mathieu Vinken ◽  
Tamara Vanhaecke ◽  
Joost van Delft ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rat Liver ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Rat Hepatocytes ◽  
Primary Rat Hepatocytes

Glucuronidation of thyroid hormone in rat liver: effects of in vivo treatment with microsomal enzyme inducers and in vitro assay conditions.

Endocrinology ◽  
1993 ◽  
Vol 133 (5) ◽  
pp. 2177-2186 ◽  
Author(s):  
T J Visser ◽  
E Kaptein ◽  
H van Toor ◽  
J A van Raaij ◽  
K J van den Berg ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Rat Liver ◽  
In Vitro Assay ◽  
Microsomal Enzyme ◽  
Vitro Assay ◽  
In Vivo Treatment ◽  
Microsomal Enzyme Inducers ◽  
Assay Conditions

Solved in vivo/in vitro discrepancy in methapyrilene induced gene alterations in rat liver and in collagen sandwich cultured primary rat hepatocytes

2009 ◽  
Vol 189 ◽  
pp. S77
Author(s):  
Markus Schug ◽  
Tanja Heise ◽  
Georgia Günther ◽  
Dorothe Storm ◽  
Axel Oberemm ◽  
...  
Keyword(s):  
Rat Liver ◽  
Rat Hepatocytes ◽  
Primary Rat Hepatocytes ◽  
Gene Alterations

13 C n. m. r. studies of gluconeogenesis in rat liver suspensions and perfused mouse livers

1980 ◽  
Vol 289 (1037) ◽  
pp. 407-411 ◽  
Keyword(s):  
Thyroid Hormone ◽  
Rat Liver ◽  
Hormone Treatment ◽  
Liver Cells ◽  
First Approximation ◽  
Rat Liver Cells

Our early 31 P n.m.r. studies of compartmentation in suspensions of rat liver cells have been extended by following fructose-1-phosphate peaks, known to be in the cytosol, which gave the same pH as the P 1 peak previously assigned to the cytosol. Gluconeogenesis has been followed from [ 13 C]glycerol labelled at C1,3 or at C2 and from labelled [3- 13 C] alanine. With the glycerol substrate it was possible to follow the label into α-glycerophosphate and to determine its distribution in the glucose formed. To a first approximation (i.e. 90 %) the glucose label could be followed from its original glycerol position, e.g. [ 1,3- 13 C]glycerol to strongly labelled positions 1, 3, 4 and 6 of glucose. Slightly more than 10% of the label was scrambled (i.e. 10% movement of C2 to C1 and ca . 10% of C1 was lost, the remainder being unchanged). These are consistent with a flux through the pentose shunt, dominated by the transketolase pathway. With [3- 13 C]alanine, about 14 resonances are assigned to different carbons of the intermediates β-hydroxybutyrate, acetoacetate, lactate, pyruvate, glutamate, glutamine, asparate, as well as C2-alanine, while another 7 resonances are observed from the different anomeric carbons of glucose. The effects of thyroid hormone treatment of the rats upon numerous in vivo rates are clearly observed and will be illustrated.

Sign in / Sign up

Export Citation Format

Share Document