Intracellular signalling of epinephrine in rat hepatocytes during fetal development and hepatic regeneration

1993 ◽  
Vol 13 (1) ◽  
pp. 53-60 ◽  
Author(s):  
S. Leoni ◽  
S. Spagnuolo ◽  
F. Terenzi ◽  
M. Marino ◽  
C. Bolaffi ◽  
...  
Keyword(s):  
Partial Hepatectomy ◽  
Calcium Concentration ◽  
Inositol Phosphates ◽  
Early Stage ◽  
Rat Hepatocytes ◽  
Calcium Transient ◽  
Cytosolic Calcium ◽  
Hepatic Regeneration ◽  
Fetal Life ◽  
M Phase

The changes in intracellular calcium concentration and IP3 production after the addition of epinephrine were analysed in adult, fetal (20th–22nd day of intrauterine life), and regenerating rat hepatocytes (4 h–24 h after partial hepatectomy) to determine whether the signal transduction is the same in quiescent proliferating and differentiating cells. The epinephrine treatment causes a significative cytosolic calcium transient in hepatocytes isolated in the last day of fetal life (22-day old) and in the early stage of regeneration (4 h). This effect is not significant in the previous stage of fetal life (20-day old) and at the onset of M phase of cell cycle after partial hepatectomy (24 h). [3H]myo inositol incorporation into IP3 and IP4 is higher in 20 day fetal and regenerating hepatocytes with respect to the control. In these cells the epinephrine does not affect basal level of IP3 and IP4, while it causes a substantial increase of these inositol phosphates in adult hepatocytes. [3H]myo inositol incorporation into PIP2 is very low at the 20th day of fetal life. Epinephrine has no effect on this parameter in fetal and regenerating hepatocytes. Our results show that the epinephrine signal is mediated differently in proliferating and in quiescent hepatocytes.

Polyamine transport systems in isolated rat hepatocytes derived from resting and regenerating livers

1992 ◽  
Vol 263 (2) ◽  
pp. G169-G173
Author(s):  
G. Y. Minuk ◽  
A. Bennaroch ◽  
L. X. Ding
Keyword(s):  
Partial Hepatectomy ◽  
Specific Binding ◽  
Rat Hepatocytes ◽  
Eukaryotic Cell ◽  
Transport Systems ◽  
Affinity Constant ◽  
Hepatic Regeneration ◽  
Gamma Aminobutyric Acid ◽  
Isolated Rat Hepatocytes ◽  
Polyamine Transport

Polyamines and their principal metabolite, gamma-aminobutyric acid (GABA), modulate eukaryotic cell growth. To determine whether the liver possesses specific polyamine transport sites and whether changes occur to these or GABA transport sites during hepatic regeneration, suspensions of rat hepatocytes derived from in situ collagenase perfusions of livers at times 0, 24, 48, and 72 h post-partial hepatectomy were incubated at 4, 20, and 37 degrees C with various concentrations of the following ligands: [3H]putrescine, [3H]spermidine, [14C]spermine, and [3H]GABA together with or without excess unlabeled ligand, KCN, ouabain, or digitoxigenin. Of the ligands studied, only [14C]spermine and [3H]GABA were associated with specific binding to hepatocytes derived from nonregenerating livers. Spermine binding correlated with the concentration of hepatocytes in the incubation mixture and reached equilibrium within 60 min. The approximate affinity constant (KD) was 5.5 x 10(-5) mol/10(6) hepatocytes, and maximum number of binding sites (Bmax) was 1.8 +/- 1.2 x 10(-7) mol.10(6) hepatocytes-1.min-1. Binding was neither temperature nor sodium dependent and was not inhibited by KCN, ouabain, digitoxigenin, other polyamines, or GABA. Aside from a 43% decrease in spermine binding at 24 h post-partial hepatectomy [5.1 +/- 1.1 vs. 8.9 +/- 3.1 x 10(3) disintegrations per minute (dpm)/10(6) hepatocytes at time 0, P less than 0.05] and a 39% decrease in GABA binding (3.4 +/- 1.3 vs. 5.5 +/- 1.9 x 10(3) dpm/10(6) hepatocytes, P less than 0.05), there were no significant changes in ligand binding during hepatic regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Silymarin Accelerates Liver Regeneration after Partial Hepatectomy

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Jia-Ping Wu ◽  
Chin-Chuan Tsai ◽  
Yu-Lan Yeh ◽  
Yueh-Min Lin ◽  
Chien-Chung Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Tissue Injury ◽  
Hepatic Regeneration ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Sprague Dawley Rats ◽  
M Phase ◽  
G2 Phase

Partial hepatectomy (PHx) is a liver regeneration physiological response induced to maintain homeostasis. Liver regeneration evolved presumably to protect wild animals from catastrophic liver loss caused by toxins or tissue injury. Silymarin (Sm) ability to stimulate liver regeneration has been an object of curiosity for many years. Silymarin has been investigated for use as an antioxidant and anticarcinogen. However, its use as a supportive treatment for liver damage is elusive. In this study, we fed silymarin (Sm, 25 mg/kg) to male Sprague-Dawley rats for 7 weeks. Surgical 2/3 PHx was then conducted on the rats at 6 hrs, 24 hrs, and 72 hrs. Western blot and RT-PCR were conducted to detect the cell cycle activities and silymarin effects on hepatic regeneration. The results showed that silymarin enhanced liver regeneration by accelerating the cell cycle in PHx liver. Silymarin led to increased G1 phase (cyclin D1/pRb), S phase (cyclin E/E2F), G2 phase (cyclin B), and M phase (cyclin A) protein and mRNA at 6 hrs, 24 hrs, and 72 hrs PHx. HGF, TGFα, and TGFβ1 growth factor expressions were also enhanced. We suggest that silymarin plays a crucial role in accelerated liver regeneration after PHx.

scholarly journals Cell-type-specific modelling of intracellular calcium signalling: a urothelial cell model

2013 ◽  
Vol 10 (86) ◽  
pp. 20130487 ◽  
Author(s):  
Peter A. Appleby ◽  
Saqib Shabir ◽  
Jennifer Southgate ◽  
Dawn Walker
Keyword(s):  
Calcium Concentration ◽  
Cell Model ◽  
Calcium Signalling ◽  
Calcium Transient ◽  
Cytosolic Calcium ◽  
Urothelial Cell ◽  
Calcium Transients ◽  
Cell Type ◽  
Key Features ◽  
Signalling Models

Calcium signalling plays a central role in regulating a wide variety of cell processes. A number of calcium signalling models exist in the literature that are capable of reproducing a variety of experimentally observed calcium transients. These models have been used to examine in more detail the mechanisms underlying calcium transients, but very rarely has a model been directly linked to a particular cell type and experimentally verified. It is important to show that this can be achieved within the general theoretical framework adopted by these models. Here, we develop a framework designed specifically for modelling cytosolic calcium transients in urothelial cells. Where possible, we draw upon existing calcium signalling models, integrating descriptions of components known to be important in this cell type from a number of studies in the literature. We then add descriptions of several additional pathways that play a specific role in urothelial cell signalling, including an explicit ionic influx term and an active pumping mechanism that drives the cytosolic calcium concentration to a target equilibrium. The resulting one-pool model of endoplasmic reticulum (ER)-dependent calcium signalling relates the cytosolic, extracellular and ER calcium concentrations and can generate a wide range of calcium transients, including spikes, bursts, oscillations and sustained elevations in the cytosolic calcium concentration. Using single-variate robustness and multivariate sensitivity analyses, we quantify how varying each of the parameters of the model leads to changes in key features of the calcium transient, such as initial peak amplitude and the frequency of bursting or spiking, and in the transitions between bursting- and plateau-dominated modes. We also show that, novel to our urothelial cell model, the ionic and purinergic P2Y pathways make distinct contributions to the calcium transient. We then validate the model using human bladder epithelial cells grown in monolayer cell culture and show that the model robustly captures the key features of the experimental data in a way that is not possible using more generic calcium models from the literature.

Influence of Telomere Length in Hepatocytes on Liver Regeneration after Partial Hepatectomy in Rats

2018 ◽  
Vol 59 (1-2) ◽  
pp. 83-90 ◽  
Author(s):  
Anne Andert ◽  
Hamid P. Alizai ◽  
Tom Florian Ulmer ◽  
Christoph Heidenhain ◽  
Patrick Ziegler ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Telomere Length ◽  
Partial Hepatectomy ◽  
Rat Hepatocytes ◽  
Liver Weight ◽  
Nuclear Antigen ◽  
Hepatic Regeneration ◽  
Older Individuals ◽  
Significant Difference ◽  
Old Rats

Background: The aim of this study was to investigate telomere length in hepatocytes as a biomarker for liver regeneration after partial hepatectomy (PH) in rats. Materials and Methods: Sixty male Wistar rats underwent a 70% PH. One-month-old rats were assigned to group Y (n = 30) and 4-month-old rats were assigned to group O (n = 30). The rats were euthanized, and their livers were then harvested at postoperative day (POD) 1, 2, 3, 4, or 7. Telomere lengths and established parameters for liver regeneration (residual liver weight and levels of proliferating cell nuclear antigen [PCNA], Ki67, and interleukin [IL]-6) were measured. Results: We observed a significant increase in residual liver weight in group Y compared to that in group O (p = 0.001). The levels of Ki67 (p = 0.016), PCNA (p < 0.0001), and IL-6 (p < 0.001) were significantly higher in group Y. Furthermore, the rats in group Y had significantly earlier peak values of Ki67 and PCNA. Telomeres were significantly longer at the time of PH in group Y (p = 0.001). We showed a correlation between telomere length at the day of PH and liver regeneration. Animals with longer telomeres at the time of PH had better liver regeneration (p = 0.015). In group Y, animals with increased liver regeneration (median cut-off: > 122%) did not show any significant difference in telomere length (p = 0.587) compared to rats with regular regeneration (< 122%). However, in the older animals, rats with increased regeneration had significantly longer telomeres (p = 0.019) than rats with regular regeneration. Conclusion: Telomere length in rat hepatocytes depends on age, and animals with long telomeres had earlier and better regeneration of healthy liver tissue than rats with short telomeres. Our data confirms that telomere length in rat hepatocytes could be used as a possible predictive marker for liver regeneration, and could help to identify older individuals with a high capacity for hepatic regeneration.

Hypersensitivity to Thromboxane A2 in Cholesterol-Rich Human Platelets

1990 ◽  
Vol 64 (04) ◽  
pp. 594-599 ◽  
Author(s):  
Takuya Tomizuka ◽  
Kyohei Yamamoto ◽  
Aizan Hirai ◽  
Yasushi Tamura ◽  
Sho Yoshida
Keyword(s):  
Calcium Concentration ◽  
Binding Capacity ◽  
Thromboxane A2 ◽  
Cytosolic Calcium ◽  
Cholesterol Content ◽  
Human Platelets ◽  
Dissociation Rate ◽  
Platelet Membrane ◽  
Maximal Concentration ◽  
Equilibrium Dissociation

SummaryThe effect of changes in platelet membrane cholesterol content on thromboxane A2 (TXA2)-induced platelet activation was studied. Concentrations of 9,ll-epithio-ll,12-methano-TXA2 (STA2), a stable analogue of TXA2 which can cause half-maximal aggregation and release of [14C]serotonin in cholesterol-rich platelets were significantly lower than those in cholesterol-normal platelets. STA2-induced increase in cytosolic calcium concentration and [32P]phosphatidic acid formation in cholesterol-rich platelets were significantly greater than those in cholesterol-normal platelets. The maximal concentration of binding site (Bmax) for SQ29548 was significantly increased in cholesterol-rich platelets compared with cholesterol-normal platelets, while the equilibrium dissociation rate constant (Kd) for SQ29548 did not differ between cholesterol-rich and cholesterol-normal platelets. The present study suggested that sensitivity to TXA2 was increased by the incorporation of cholesterol into platelet membrane and that the cause of hypersensitivity to TXA2 in cholesterol-rich platelets may be partly explained by an increase in binding capacity for TXA2.

scholarly journals Synthetic lipopeptide Pam3CysSer(Lys)4 is an effective activator of human platelets

1994 ◽  
Vol 266 (6) ◽  
pp. C1684-C1691 ◽  
Author(s):  
M. Berg ◽  
S. Offermanns ◽  
R. Seifert ◽  
G. Schultz
Keyword(s):  
Calcium Concentration ◽  
Cytosolic Calcium ◽  
Human Platelets ◽  
Cellular Effects ◽  
Prostacyclin Receptor ◽  
Serotonin Secretion ◽  
Peptide Moiety ◽  
Lipid Moiety ◽  
Molecular Masses ◽  
Aggregation Of Platelets

Lipopeptide analogues of the NH2-terminus of bacterial lipoprotein are known to induce activation of macrophages, neutrophils, and lymphocytes. We studied the effect of the lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-( S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine [Pam3CysSer(Lys)4] on several functions of human platelets. Pam3CysSer(Lys)4 led to the aggregation of platelets and induced the secretion of serotonin with an effectiveness similar to thrombin. These cellular effects of Pam3CysSer(Lys)4 were concentration dependent, being half maximal at 2-3 microM and maximal at 10-30 microM. Another lipopeptide also induced platelet aggregation and serotonin secretion but was less potent and less effective than Pam3CysSer(Lys)4. The lipid moiety and the peptide moiety of Pam3CysSer(Lys)4 alone were without any effect. Lipopeptides also stimulated tyrosine phosphorylation of several proteins with molecular masses similar to those found to be tyrosine phosphorylated in response to thrombin, and Pam3CysSer(Lys)4 led to an increase in the cytosolic calcium concentration. All studied responses of platelets to lipopeptides were inhibited by the prostacyclin receptor agonist cicaprost. Taken together, our data show that lipopeptides are effective activators of human platelets and that this activation is susceptible to the action of physiological platelet inhibitors.

Hepatocellular expression of glucose-6-phosphatase is unaltered during hepatic regeneration

1998 ◽  
Vol 275 (4) ◽  
pp. G717-G722 ◽  
Author(s):  
Wisam F. Zakko ◽  
Carl L. Berg ◽  
John L. Gollan ◽  
Richard M. Green
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Protein Expression ◽  
Partial Hepatectomy ◽  
Initial Phase ◽  
Physiological Function ◽  
Liver Homogenate ◽  
Hepatic Regeneration ◽  
Mrna Levels ◽  
Microsomal Enzyme

Gluconeogenesis and glycogenolysis are essential hepatic functions required for glucose homeostasis. During the initial phase of hepatic regeneration, the immediate-early genes (IEG) are rapidly expressed, and the IEG RL-1 encodes for glucose-6-phosphatase (G-6- Pase). G-6- Pase is a microsomal enzyme essential for gluconeogenesis and glycogenolysis. This study employs a partial-hepatectomy model to examine the expression and activity of G-6- Pase. After partial hepatectomy, rat hepatic G-6- Pase gene expression is transcriptionally regulated, and mRNA levels are increased ≈30-fold. However, in contrast to this rapid gene induction, microsomal enzyme activity is unchanged after partial hepatectomy. Western blotting demonstrates that microsomal G-6- Pase protein expression is also unchanged after partial hepatectomy, and similar results are also noted in whole liver homogenate. Thus, despite marked induction in gene expression of the IEG G-6- Pase after partial hepatectomy, protein expression and enzyme activity remain unchanged. These data indicate that, although this hepatocyte IEG is transcriptionally regulated, the physiologically important level of regulation is posttranscriptional. This highlights the importance of correlating gene expression of IEG with protein expression and physiological function.

scholarly journals Cerium oxide nanoparticles improve liver regeneration after acetaminophen-induced liver injury and partial hepatectomy in rats

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Bernat Córdoba-Jover ◽  
Altamira Arce-Cerezo ◽  
Jordi Ribera ◽  
Montse Pauta ◽  
Denise Oró ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Regeneration ◽  
Cerium Oxide ◽  
Partial Hepatectomy ◽  
Experimental Models ◽  
Cerium Oxide Nanoparticles ◽  
Hepatic Regeneration ◽  
Oxide Nanoparticles ◽  
Acetyl Cysteine

Abstract Background and aims Cerium oxide nanoparticles are effective scavengers of reactive oxygen species and have been proposed as a treatment for oxidative stress-related diseases. Consequently, we aimed to investigate the effect of these nanoparticles on hepatic regeneration after liver injury by partial hepatectomy and acetaminophen overdose. Methods All the in vitro experiments were performed in HepG2 cells. For the acetaminophen and partial hepatectomy experimental models, male Wistar rats were divided into three groups: (1) nanoparticles group, which received 0.1 mg/kg cerium nanoparticles i.v. twice a week for 2 weeks before 1 g/kg acetaminophen treatment, (2) N-acetyl-cysteine group, which received 300 mg/kg of N-acetyl-cysteine i.p. 1 h after APAP treatment and (3) partial hepatectomy group, which received the same nanoparticles treatment before partial hepatectomy. Each group was matched with vehicle-controlled rats. Results In the partial hepatectomy model, rats treated with cerium oxide nanoparticles showed a significant increase in liver regeneration, compared with control rats. In the acetaminophen experimental model, nanoparticles and N-acetyl-cysteine treatments decreased early liver damage in hepatic tissue. However, only the effect of cerium oxide nanoparticles was associated with a significant increment in hepatocellular proliferation. This treatment also reduced stress markers and increased cell cycle progression in hepatocytes and the activation of the transcription factor NF-κB in vitro and in vivo. Conclusions Our results demonstrate that the nanomaterial cerium oxide, besides their known antioxidant capacities, can enhance hepatocellular proliferation in experimental models of liver regeneration and drug-induced hepatotoxicity.

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