Expression of Glutamine Synthetase and Carbamoylphosphate Synthetase I in a Bioartificial Liver: Markers for the Development of Zonation in vitro

2008 ◽  
Vol 188 (3) ◽  
pp. 259-269 ◽  
Author(s):  
Paul P.C. Poyck ◽  
Ruurdtje Hoekstra ◽  
Jacqueline L.M. Vermeulen ◽  
Albert C.W.A. van Wijk ◽  
Robert A.F.M. Chamuleau ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Bioartificial Liver ◽  
Carbamoylphosphate Synthetase ◽  
Liver Markers

scholarly journals Glutamine synthetase as a central element in hepatic glutamine and ammonia metabolism: novel aspects

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Benedikt Frieg ◽  
Boris Görg ◽  
Holger Gohlke ◽  
Dieter Häussinger
Keyword(s):  
Glutamine Synthetase ◽  
Protein Function ◽  
Nitrosative Stress ◽  
Point Mutations ◽  
Central Element ◽  
Ph Sensitive ◽  
Tyrosine Nitration ◽  
Ammonia Metabolism ◽  
Functional Consequences

Abstract Glutamine synthetase (GS) in the liver is expressed in a small perivenous, highly specialized hepatocyte population and is essential for the maintenance of low, non-toxic ammonia levels in the organism. However, GS activity can be impaired by tyrosine nitration of the enzyme in response to oxidative/nitrosative stress in a pH-sensitive way. The underlying molecular mechanism as investigated by combined molecular simulations and in vitro experiments indicates that tyrosine nitration can lead to a fully reversible and pH-sensitive regulation of protein function. This approach was also used to understand the functional consequences of several recently described point mutations of human GS with clinical relevance and to suggest an approach to restore impaired GS activity.

Primary culture of rat hepatocytes entrapped in cylindrical collagen gels: An in vitro system with application to the bioartificial liver

1992 ◽  
Vol 10 (3) ◽  
pp. 205-215 ◽  
Author(s):  
Scott L. Nyberg ◽  
Russell A. Shatford ◽  
William D. Payne ◽  
Wei-Shou Hu ◽  
Frank B. Cerra
Keyword(s):  
Primary Culture ◽  
Rat Hepatocytes ◽  
Bioartificial Liver ◽  
Collagen Gels ◽  
In Vitro System

In vitro evaluation method of bioartificial liver function: constant infusion test

2002 ◽  
Vol 5 (4) ◽  
pp. 284-288
Author(s):  
Y. G. Park ◽  
H. Iwata ◽  
T. Sajiki ◽  
H. Maeda ◽  
Y. Ueda ◽  
...  
Keyword(s):  
Liver Function ◽  
Evaluation Method ◽  
Bioartificial Liver ◽  
Constant Infusion ◽  
Infusion Test ◽  
In Vitro Evaluation ◽  
Function Constant

scholarly journals Inhibition of glutamine synthetase in monocytes from patients with acute-on-chronic liver failure resuscitates their antibacterial and inflammatory capacity

Gut ◽  
2018 ◽  
Vol 68 (10) ◽  
pp. 1872-1883 ◽  
Author(s):  
Hannelie Korf ◽  
Johannie du Plessis ◽  
Jos van Pelt ◽  
Sofie De Groote ◽  
David Cassiman ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Liver Failure ◽  
Bacterial Infections ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Phenotypic Characterisation ◽  
Severity Scores ◽  
Aclf Patient

ObjectiveAcute-on-chronic liver failure (ACLF) is associated with dysfunctional circulating monocytes whereby patients become highly susceptible to bacterial infections. Here, we identify the pathways underlying monocyte dysfunction in ACLF and we investigate whether metabolic rewiring reinstates their phagocytic and inflammatory capacity.DesignFollowing phenotypic characterisation, we performed RNA sequencing on CD14+CD16− monocytes from patients with ACLF and decompensated alcoholic cirrhosis. Additionally, an in vitro model mimicking ACLF patient-derived features was implemented to investigate the efficacy of metabolic regulators on monocyte function.ResultsMonocytes from patients with ACLF featured elevated frequencies of interleukin (IL)-10-producing cells, reduced human leucocyte antigen DR isotype (HLA-DR) expression and impaired phagocytic and oxidative burst capacity. Transcriptional profiling of isolated CD14+CD16− monocytes in ACLF revealed upregulation of an array of immunosuppressive parameters and compromised antibacterial and antigen presentation machinery. In contrast, monocytes in decompensated cirrhosis showed intact capacity to respond to inflammatory triggers. Culturing healthy monocytes in ACLF plasma mimicked the immunosuppressive characteristics observed in patients, inducing a blunted phagocytic response and metabolic program associated with a tolerant state. Metabolic rewiring of the cells using a pharmacological inhibitor of glutamine synthetase, partially restored the phagocytic and inflammatory capacity of in vitro generated- as well as ACLF patient-derived monocytes. Highlighting its biological relevance, the glutamine synthetase/glutaminase ratio of ACLF patient-derived monocytes positively correlated with disease severity scores.ConclusionIn ACLF, monocytes feature a distinct transcriptional profile, polarised towards an immunotolerant state and altered metabolism. We demonstrated that metabolic rewiring of ACLF monocytes partially revives their function, opening up new options for therapeutic targeting in these patients.

scholarly journals Rhophilin-2 Upregulates Glutamine Synthetase by Stabilizing c-Myc Protein and Confers Resistance to Glutamine Deprivation in Lung Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Dakai Xiao ◽  
Jiaxi He ◽  
Zhihua Guo ◽  
Huiming He ◽  
Shengli Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Glutamine Synthetase ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Clinical Sample ◽  
Glutamine Metabolism ◽  
Lung Cancer Cells ◽  
Mesenchymal Transformation ◽  
Proliferation And Invasion

IntroductionRHPN2, a member of rhophilin family of rho-binding proteins, regulates actin cytoskeleton and vesicular trafficking, and promotes mesenchymal transformation in cancer. We have found that RHPN2 was significantly mutated in lung adenocarcinoma (LUAD). However, the role of RHPN2 in lung cancer is not fully understood.MethodsIn the present study, we investigated the expression of RHPN2 in 125 patients with LUAD by qRT-PCR and correlated its expression with clinical characteristics. The effects of RHPN2 on the proliferation and invasion of lung cancer cells were determined by CCK-8 and in vitro transwell assays, clonogenic assay, and xenograft mouse model. The RhoA pull down assay and Western blotting were performed to elucidate the mechanism of RNPN2 in tumorigenesis of lung cancer.ResultsRHPN2 was overexpressed in tumors from LUAD, and high levels of RHPN2 were associated with poor prognosis of LUAD patients. RHPN2 was required for proliferation and invasion of lung cancer cells. Intriguingly, overexpression of RHPN2 conferred the resistance to glutamine depletion in lung cancer cells. Mechanistic studies revealed that ectopic overexpression of RHPN2 promoted the stability of c-Myc protein via phosphorylation at Ser62 and increased c-Myc target glutamine synthetase (GS). Analysis of GS expression in clinical sample showed that the expression of GS was elevated in tumor cells. Kaplan-Meier analysis revealed that high levels of GS were significantly associated with worse overall survival time of the patients with LUAD.ConclusionsTaken together, this study suggested that RHPN2 was involved in tumorigenesis of lung cancer via modulating c-Myc stability and the expression of its target GS in lung adenocarcinoma, which links RHPN2 and glutamine metabolism.

scholarly journals Impact of A Cargo-Less Liposomal Formulation on Dietary Obesity-Related Metabolic Disorders in Mice

2020 ◽  
Vol 21 (20) ◽  
pp. 7640
Author(s):  
Varsha Komalla ◽  
Behjat Sheikholeslami ◽  
Gerard Li ◽  
Bishwajit Bokshi ◽  
Yik Lung Chan ◽  
...  
Keyword(s):  
Weight Control ◽  
Single Agent ◽  
Macrophage Infiltration ◽  
Pharmacological Intervention ◽  
Tissue Macrophage ◽  
Dietary Obesity ◽  
Liver Markers ◽  
Underlying Inflammation

Current therapeutic options for obesity often require pharmacological intervention with dietary restrictions. Obesity is associated with underlying inflammation due to increased tissue macrophage infiltration, and recent evidence shows that inflammation can drive obesity, creating a feed forward mechanism. Therefore, targeting obesity-induced macrophage infiltration may be an effective way of treating obesity. Here, we developed cargo-less liposomes (UTS-001) using 1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC (synthetic phosphatidylcholine) as a single-agent to manage weight gain and related glucose disorders due to high fat diet (HFD) consumption in mice. UTS-001 displayed potent immunomodulatory properties, including reducing resident macrophage number in both fat and liver, downregulating liver markers involved in gluconeogenesis, and increasing marker involved in thermogenesis. As a result, UTS-001 significantly enhanced systemic glucose tolerance in vivo and insulin-stimulated cellular glucose uptake in vitro, as well as reducing fat accumulation upon ad libitum HFD consumption in mice. UTS-001 targets tissue residence macrophages to suppress tissue inflammation during HFD-induced obesity, resulting in improved weight control and glucose metabolism. Thus, UTS-001 represents a promising therapeutic strategy for body weight management and glycaemic control.

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