353 Effects of Bile Acids on Translocator Protein Expression in the Azoxymethane Model of Hepatic Encephalopathy

2016 ◽  
Vol 150 (4) ◽  
pp. S1027
Author(s):  
Juan P. Diocares ◽  
Matthew McMillin ◽  
Rebecca Haines ◽  
Gabriel Frampton ◽  
Stephanie Grant ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Protein Expression ◽  
Bile Acids ◽  
Translocator Protein

scholarly journals Increased cholesterol 7α-hydroxylase expression and size of the bile acid pool in the lactating rat

2008 ◽  
Vol 294 (4) ◽  
pp. G1009-G1016 ◽  
Author(s):  
Clavia Ruth Wooton-Kee ◽  
David E. Cohen ◽  
Mary Vore
Keyword(s):  
Bile Acid ◽  
Protein Expression ◽  
Mrna Expression ◽  
Bile Acids ◽  
Fold Increase ◽  
Bile Acid Pool ◽  
Hydrophobicity Index ◽  
Acid Pool ◽  
Bile Acid Transporters ◽  
Cholic Acids

Maximal bile acid secretory rates and expression of bile acid transporters in liver and ileum are increased in lactation, possibly to facilitate increased enterohepatic recirculation of bile acids. We determined changes in the size and composition of the bile acid pool and key enzymes of the bile acid synthetic pathway [cholesterol 7α-hydroxylase (Cyp7a1), sterol 27-hydroxylase (Cyp27a1), and sterol 12α-hydroxylase (Cyp8b1)] in lactating rats relative to female virgin controls. The bile acid pool increased 1.9 to 2.5-fold [postpartum (PP) days 10, 14, and 19–23], compared with controls. A 1.5-fold increase in cholic acids and a 14 to 20% decrease in muricholic acids in lactation significantly increased the hydrophobicity index. In contrast, the hepatic concentration of bile acids and small heterodimer partner mRNA were unchanged in lactation. A 2.8-fold increase in Cyp7a1 mRNA expression at 16 h (10 h of light) demonstrated a shift in the diurnal rhythm at day 10 PP; Cyp7a1 protein expression and cholesterol 7α-hydroxylase activity were significantly increased at this time and remained elevated at day 14 PP but decreased to control levels by day 21 PP. There was an overall decrease in Cyp27a1 mRNA expression and a 20% decrease in Cyp27a1 protein expression, but there was no change in Cyp8b1 mRNA or protein expression at day 10 PP. The increase in Cyp7a1 expression PP provides a mechanism for the increase in the bile acid pool.

Inhibition of interferon-α-induced signaling by hyperosmolarity and hydrophobic bile acids

2010 ◽  
Vol 391 (10) ◽  
Author(s):  
Dirk Graf ◽  
Katrin Haselow ◽  
Ivo Münks ◽  
Johannes G. Bode ◽  
Dieter Häussinger
Keyword(s):  
Protein Expression ◽  
Bile Acids ◽  
Hepatoma Cell ◽  
Protein A ◽  
Sodium Taurocholate ◽  
Inhibitory Effect ◽  
Interferon Α ◽  
Hepatoma Cell Line ◽  
Human Hepatoma Cell ◽  
Mrna And Protein Expression

Abstract Apart from viral conditions, host factors such as elevated bile acid concentrations are determinants of successful interferon-α (IFN-α) treatment in patients with chronic hepatitis C or B. The present study demonstrates that hydrophobic bile acids inhibit Jak1- and Tyk2-phosphorylation, which lead to blockade of STAT1-mediated IFN-α-signaling in the sodium-taurocholate cotransporting peptide (NTCP)-transfected human hepatoma cell line HepG2, resulting in a decreased mRNA and protein expression of IFN-stimulated genes such as myxovirus resistance protein A (MxA) or dsRNA-activated protein kinase (PKR). In addition, hyperosmotic stress leads to an inhibition of IFN-α-induced Jak1- and Tyk2-phosphorylation, and STAT1/STAT2-phosphorylation and gene expression. This inhibitory effect of hydrophobic bile acids or hyperosmolarity is not due to caspase-mediated cleavage or lysosomal degradation of the cognate receptors or to the generation of oxidative stress, activation of p38- or Erk-mediated MAPK pathways or phosphatase activity. Preincubation with the organic osmolyte betaine blocked the inhibitory effect of bile acids or hyperosmolarity on MxA protein expression, but had no effect on transcript levels or activation of STAT1, suggesting that betaine mediates its effects on MxA expression at a translational or post-translational level. Our findings could provide a rationale for betaine use in cholestatic HBV/HCV patients undergoing interferon therapy.

scholarly journals The Bile Acids Specifically Modulate Colonic MUC2 and Tight Junction Protein Expression in the Human Colon Cancer Cell Line

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 33-33
Author(s):  
Yafang Ma ◽  
Zixin Huang ◽  
Chunbao Li
Keyword(s):  
Bile Acid ◽  
Protein Expression ◽  
Tight Junction ◽  
Bile Acids ◽  
Human Colon ◽  
Tight Junction Protein ◽  
Human Colon Cancer ◽  
Tight Junction Protein Expression ◽  
Junction Protein ◽  
Muc2 Expression

Abstract Objectives Alterations to mucin secretion and epithelial tight junctions can compromise the ability of the epithelium to act as a barrier for the host to prevent pathogenic attack. Bile acids are synthesized in hepatocytes and released into the intestine, further modified by gut bacteria. Although many studies have investigated the changes of intestinal bile acids in the pathogenesis of various immune disorders, there are few reports about its function in preventing or interventing the dysfunction of the intestinal barrier. In this study, we sought to investigate the effects of the colonic bile acids on MUC2 and tight junction protein expression, which are crucial to colonic barrier. Methods Regulation of MUC2 and tight junction protein expression was assayed in the human colon cancer LS174T and T84 cells. The cells were treated with deoxycholic acid (DCA), lithocholic acid (LCA), 3-oxo-DCA, 3-oxo-LCA, isoDCA and isoLCA (100 μM or 200 μM), respectively. Proliferation of the cells was investigated with the MTT assay. mRNA expression of MUC2, ZO-1, occludin, claudin1 were measured by RT-PCR. Nuclear bile acid receptor FXR and TGR5, toll-like receptors and TLR adaptor MyD88, and genes (CDX2, AGR2, MyD88) related to mucin synthesis and secretion were also measured. Results In comparison with the untreated control, DCA, 3-oxo-DCA, isoDCA and isoLCA (100 μM) significantly upregulated the ZO-1, occludin and bile acid receptor FXR gene expression in the T84 cell. LCA, 3-oxo-LCA and isoLCA upregulated MUC2 expression at 200 μM, but showed no significant effect at 100 μM. DCA only significantly upregulated MUC2 expression at 200 μM, but isoDCA upregulated MUC2 expression independent of concentration in the LS174T cell. The expression of CDX2, AGR2, MyD88 was consistent with MUC2. Conclusions Bile acids at various concentrations specifically modulate MUC2 and tight junction protein expression, and thereby alter the colonic barrier function. This regulatory effect of bile acids could be mediated by activating bile acid receptors FXR. Funding Sources This work was financially supported by Ministry of Science and Technology of China (10000 Talent Project).

P.0253 Two-week lithium treatment modulates translocator protein expression in brain regions in the animal models of acute bipolar episodes

2021 ◽  
Vol 53 ◽  
pp. S184-S185
Author(s):  
K. Sakrajda ◽  
D. Szczepankiewicz ◽  
J. Nowakowska ◽  
P. Zakowicz ◽  
J. Pawlak ◽  
...  
Keyword(s):  
Animal Models ◽  
Protein Expression ◽  
Lithium Treatment ◽  
Brain Regions ◽  
Translocator Protein

In vitro Effects of the Specific Mitochondrial TSPO Ligand Ro5 4864 in Cultured Human Osteoblasts

2017 ◽  
Vol 126 (02) ◽  
pp. 77-84 ◽  
Author(s):  
Nahum Rosenberg ◽  
Orit Rosenberg ◽  
Abraham Weizman ◽  
Leo Veenman ◽  
Moshe Gavish
Keyword(s):  
Protein Expression ◽  
Cellular Proliferation ◽  
Protoporphyrin Ix ◽  
Anion Channel ◽  
Translocator Protein ◽  
Mitochondrial Activity ◽  
Voltage Dependent Anion Channel ◽  
Hexokinase 2 ◽  
Human Osteoblasts

AbstractThe 18 kDa mitochondrial translocator protein (TSPO) ligands (10 µM), e. g., protoporphyrin IX, PK 11195 and FGIN-1-27, have different effects on metabolism and protein expression in human osteoblasts. In this study, we investigated the archetypical TSPO specific ligand Ro5-4864 (10 µM) effect in primary osteoblasts in culture aiming to further understand the TSPO role in these mature metabolically active cells.We found that following exposure to Ro5-4864, cellular [18F]-FDG incorporation and ATP content were reduced by 48% (p<0.001) and 44% (p<0.001), respectively. The mitochondrial membrane potential (ΔΨm) increased by 50% (p<0.01), mRNA synthesis of TSPO and voltage dependent anion channel (VDAC1) decreased both by 70%, the TSPO and VDAC1 protein expression decreased by 80% and 68%, respectively (p<0.001). Ro5 4864 caused a decrease in the proportion of cells in the G1 phase (by 20%, p<0.05), shifting the cell cycle to the S and G2/M phases. Furthermore, 63% decrease in hexokinase 2 protein expression (p<0.001) was found. However, we found no significant effects on hexokinase 2 mRNA expression (by RT-PCR). We also did not see significant changes in mitochondrial mass (MitoTracker Green assay), apoptosis rate (TUNEL assay), overall cell death (LDH assay), cellular proliferation (BrdU assay), cell maturation (cellular alkaline phosphatase assay), and the number of cells in the culture.Therefore, an overall effect of Ro5-4864 exhorts is via pathways related to the mitochondrial activity, which is only partly like PK 11195, but not to the other TSPO ligands.

scholarly journals A Current Review of the Diagnostic and Treatment Strategies of Hepatic Encephalopathy

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Z. Poh ◽  
P. E. J. Chang
Keyword(s):  
Hepatic Encephalopathy ◽  
Clinical Symptoms ◽  
Treatment Strategies ◽  
Benzodiazepine Receptor ◽  
Minimal Hepatic Encephalopathy ◽  
Current Treatment ◽  
Translocator Protein ◽  
Diagnostic Tools ◽  
Neuropsychiatric Manifestations

Hepatic encephalopathy (HE) is a serious and potentially fatal complication in patients with cirrhotic liver disease. It is a spectrum ranging from minimal hepatic encephalopathy (MHE) without recognizable clinical symptoms or signs, to overt HE with risk of cerebral edema and death. HE results in diminished quality of life and survival. The broad range of neuropsychiatric manifestations reflects the range of pathophysiological mechanisms and impairment in neurotransmission that are purported to cause HE including hyperammonemia, astrocyte swelling, intra-astrocytic glutamine, upregulation of 18-kDa translocator protein (TSPO) (formerly known as peripheral benzodiazepine receptor or PBTR), and manganese. There is a myriad of diagnostic tools including simple bedside clinical assessment, and more complex neuropsychological batteries and neurophysiological tests available today. Current treatment strategies are directed at reducing ammonia, with newer agents showing some early promise. This paper describes the pathophysiology of the disease and summarises current diagnostic and treatment therapies available.

scholarly journals High Rumen-Degradable Starch Diet Promotes Hepatic Lipolysis and Disrupts Enterohepatic Circulation of Bile Acids in Dairy Goats

2020 ◽  
Vol 150 (10) ◽  
pp. 2755-2763
Author(s):  
Jing Shen ◽  
Xiaoying Han ◽  
Lixin Zheng ◽  
Shimin Liu ◽  
Chunjia Jin ◽  
...  
Keyword(s):  
Protein Expression ◽  
Bile Acids ◽  
Milk Fat ◽  
Enterohepatic Circulation ◽  
Rumen Fluid ◽  
Liver Protein ◽  
Dairy Goats ◽  
Linear Discriminant ◽  
Lactating Goats ◽  
Carnitine Palmitoyltransferase 1

ABSTRACT Background High rumen-degradable starch (RDS) diets decrease milk fat. The increase of LPS in plasma associated with increased RDS impairs liver function, immune response and lipid metabolism, which depress the precursors for milk fat. Objective This study investigated the mechanism of depression of milk fat precursors in the liver and small intestine of dairy goats fed different RDS diets. Method Eighteen Guanzhong lactating goats (second lactation, 45.8 ± 1.54 kg) and 6 ruminally cannulated dairy goats (aged 2–3 y, 54.0 ± 2.40 kg) were fed 3 different diets with low dietary RDS concentrations of 20.52% (LRDS), medium RDS of 22.15% (MRDS), and high RDS of 24.88% (HRDS) for 36 and 21 d, respectively, in experiments 1 and 2. The liver metabolites and jejunal microbiota in experiment 1 and LPS concentrations in rumen fluid and plasma in experiment 2 were measured. One-way ANOVA was used to analyze the biochemical parameters and mRNA or protein expression. The MIXED procedure was used to analyze LPS concentrations. Results In experiment 1, the HRDS diet showed increased activity of alkaline phosphatase (27.4 to 41.4 U/L) in plasma (P &lt; 0.05) compared with LRDS treatment. The HRDS diet significantly increased the hepatic concentrations of l-carnitine (129%), l-palmitoylcarnitine (306%), taurochenodeoxycholate (856%), and taurodeoxycholic acid (588%) in liver (variable importance in the projection &gt; 1, P &lt; 0.10) compared with the LRDS treatment. Goats fed the HRDS diet had 33.6% greater liver protein expression of carnitine palmitoyltransferase-1 (P &lt; 0.05), and greater relative abundance of Firmicutes and Ruminococcus 2 in the jejunal content (linear discriminant analysis &gt; 2.0, P &lt; 0.05) than did goats fed LRDS diet. In experiment 2, goats fed the HRDS diet had greater LPS concentrations in rumen fluid (7.57 to 13.6 kEU/mL) and plasma (0.037 to 0.179 EU/mL) (P &lt; 0.05) than did goats fed LRDS diet. Conclusions Feeding the HRDS diet promoted hepatic lipid β-oxidation and disrupted phospholipid and bile acids metabolisms in liver, thereby reducing the supply of lipogenic precursors to the mammary gland in dairy goats.

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