1,721,035 research outputs found
The lobular expression of the rat asialoglycoprotein receptor is regulated at post-transcriptional level
No full textThe purpose of this study was to define the distribution of the asialoglycoprotein receptor (ASGP-R) main peptide, rat hepatic lectin (RHL)-1, within the rat liver lobule and to investigate its possible modulation in physiological states characterised by marked changes of receptorial expression. In particular, we chose livers from rats partially hepatectomised or at the end of pregnancy, as models, respectively, of decreased or increased expression of the ASGP-R, and used the in situ hybridisation and immunocytochemistry techniques to analyse in parallel the lobular distributions of RHL-1 mRNA and protein. In normal rat liver, although the RHL-1 mRNA was homogeneously distributed, the RHL-1 peptide was predominantly localised on the surface of pericentral hepatocytes with a gradient of expression towards the periportal zone. This gradient of expression of RHL-1 peptide was reduced in regenerating livers, in which the positive stain was restricted to a few layers of cells around the central vein. In contrast, livers at the end of pregnancy showed an overall increase of the peptide with a concomitant flattening of the gradient across the liver plate. In all the conditions, we never observed important changes in the pattern of expression of the specific mRNA. These findings indicate that the distribution of ASGP-R is heterogeneous across the liver lobule, with a pattern of expression prevalently modulated at the posttranscriptional level
Retinoic acid modulates gap junctional intercellular communication in hepatocytes and hepatoma cells
No full textMultiple parameters are involved in the effects of cadmium on prenatal hepatocytes
No full textCadmium, a toxic heavy metal, expresses its toxicity by affecting several cellular functions, such as enzyme activities, DNA repair systems, redox state of the cell and signal transduction. Although the liver is a known target organ, the mechanisms involved in cadmium toxicity are not yet clarified, especially during prenatal development. Here we consider the effects of cadmium on viability, proliferation, adhesion and defence mechanisms in primary adult and fetal rat hepatocytes. Fetal hepatocytes are less sensitive to cadmium toxicity, they appear to be unaffected or even stimulated by treatments that strongly inhibit DNA synthesis in adult cells. The behaviour of proteins involved in cell cycle regulation also differs from adult cells, according to the proliferative state. In addition, following Cd exposure, E-cadherin/beta-catenin complex disassembles in both cell types, with fetal cells being influenced at higher doses. The beta-catenin is not found in the nucleus, ruling out a direct role on DNA synthesis stimulation. Finally, metallothionein is more easily inducible in fetal hepatocytes, while Cd intracellular concentrations and HSP protein levels are not differentially affected. In conclusion, multiple cellular targets are affected by Cd in primary hepatocytes and the adverse effects of the metal are always better counteracted by fetal cells
Expression pattern of apolipoprotein E (apoE) mRNA within the rat liver acinus by in situ hybridization
No full textEffect of zinc deficiency on neutrophil transmigration and junction proteins distribution in Caco-2
No full textEffect of Fructose and 3,5-Diiodothyronine (3,5-T2) on Lipid Accumulation and Insulin Signalling in Non-Alcoholic Fatty Liver Disease (NAFLD)-Like Rat Primary Hepatocytes
No full textNon-alcoholic fatty liver disease (NAFLD) is nowadays considered as one of the most serious pathological conditions affecting the liver. NAFLD is supposed to be initiated by the accumulation of lipids in the liver, which finally results in an impaired hepatic insulin signalling. Many researchers have recently focused their attention on the role played by fructose as a NAFLD-triggering agent, because of the increased diffusion of fructose-sweetened food. However, epidemiological data do not permit to evaluate the role of fructose per se, because these foods are often associated with elevated energy intake and unhealthy lifestyle. In the present work, we analysed the effects of fructose on the accumulation of lipids and insulin signalling in rat primary hepatocytes. Moreover, we investigated the effect of the thyroid hormone metabolite, devoid of thyrotoxic effects, 3,5-diiodothyronine (3,5-T 2) over the same parameters. To evaluate the effect on insulin signalling we took into consideration three key proteins, such as p85 subunit of phosphatidylinositol 3-kinase (PI3K), phosphatase and tensin homolog (PTEN), and Akt. Our results show that fructose in vitro, in the range of physiological concentrations, was not able to stimulate either lipid accumulation or to impair insulin signalling in our NAFLD-like rat primary hepatocytes. Our data thus support the idea that fructose per se may exert detrimental effects mainly triggering systemic effects, rather than directly affecting isolated hepatocytes. Moreover, we demonstrated that 3,5-T2, at physiological levels, reduces lipid content and triggers phosphorylation of Akt in an insulin receptor-independent manner, revealing new interesting properties as a biologically active molecule.©Georg Thieme Verlag KG Stuttgart. New York
Hypertonic stress regulates amino acid transport and cell cycle proteins in chick embryo hepatocytes
No full textHyperosmotic stress affects cell growth and causes a decrease in cell volume and an increase in the uptake of organic osmolytes; however, the sensitivity of embryonic cells to osmotic treatment remain to be established. In this study we analyzed some aspects of cell cycle control and amino acid transport in hypertonic conditions during prenatal life. The effects of hyperosmotic stress on aminoacid uptake mediated by system A and on 3H-thymidine incorporation, and on the regulation of cell cycle proteins were analyzed in chick embryo hepatocytes. Hypertonic stress was able to increase system A activity and to cause cell cycle delay. Effects on amino acid transport involved p38 kinase activation and new carrier synthesis. Cyclin D1, cdk4 and PCNA levels decreased, while cyclin E, p21 and p53 levels were unchanged. Incorporation of 3H-leucine revealed a decreased synthesis of cyclin D1 protein. In contrast, the analysis of mRNA by qRT-PCR showed a net increase of cyclin D1 transcript, suggesting post-transcriptional regulation. Our data show that chick embryo hepatocytes respond to hyperosmotic conditions by arresting cell growth to prevent DNA damage and by increasing osmolyte uptake to regulate cell volume, indicating that the adaptive response to environmental stress is already present during prenatal lif
Rffect of a high cholesterol diet on DNA -synthesis during the first cell-cycle of rat liver regeneration
No full textPhosphodiesterase 4 specific inhibitors control cell growth of human hepatoma HepG2 cells
No full textCyclic nucleotides, as part of the signal transduction system, play a key role in coordinating many cellular
functions. eir involvement in the control of cell proliferation is widely recognized. Cyclic nucleotide
levels are regulated by the action of cyclases as biosynthetic enzymes, and of phosphodiesterases (PDEs)
as degradative enzymes. It is well known that in different cell types the increase of the intracellular
concentration of cyclic nucleotides leads to many physiological changes, including blockade of cell
proliferation and induction of cell differentiation.
In this study, we investigated the effects of PDE inhibitors on the growth of human hepatoma HepG2 cells.
Previous experiments showed a significant control of cell proliferation with the use of PDE4 inhibitors,
such as rolipram and DCTA-46. Treatment of HepG2 cells with 100 μM rolipram or 1 μM DC-TA-46
caused a marked increase of cAMP, 6 and 2.7 fold respectively. e effects of a permanent increase of cyclic
nucleotides were also investigated in these cells using dbcAMP as a membrane permeant-unhydrolysed
cAMP analogue. Dose-response experiments showed dose- and time-dependent effects of PDE-inhibitors
on cell growth. e concentrations of inhibitors that halved cell numbers after 96 h of treatment were used
for subsequent experiments and were: 1 μM for DC-TA-46, 100 μM for rolipram, and 1mM for dbcAMP.
Treatment with rolipram and especially with dbcAMP induced apoptosis as demonstrated by DNA
fragmentation following DAPI staining and cytofluorimetric assays. In addition, all the inhibitors produced
a decrease in cyclin D1 that was highly significant in dbcAMP-treated cells; dbcAMP also caused a slight
decline of cyclin A.
e results demonstrate an involvement of PDE inhibitors in cell cycle control and suggest that they might
be useful as potential chemotherapeutic and/or chemopreventive agents in hepatocellular carcinoma
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