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Hepatocyte polarity

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https://www.readbyqxmd.com/read/28272754/hyperpolarized-%C3%AE-1-13-c-gluconolactone-as-a-probe-of-the-pentose-phosphate-pathway
#1
Karlos X Moreno, Crystal E Harrison, Matthew E Merritt, Zoltan Kovacs, Craig R Malloy, A Dean Sherry
The pentose phosphate pathway (PPP) is thought to be upregulated in trauma (to produce excess NADPH) and in cancer (to provide ribose for nucleotide biosynthesis), but simple methods for detecting changes in flux through this pathway are not available. MRI of hyperpolarized (13) C-enriched metabolites offers considerable potential as a rapid, non-invasive tool for detecting changes in metabolic fluxes. In this study, hyperpolarized δ-[1-(13) C]gluconolactone was used as a probe to detect flux through the oxidative portion of the pentose phosphate pathway (PPPox ) in isolated perfused mouse livers...
March 8, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28272428/secreted-ectodomain-of-siglec-9-and-mcp-1-synergistically-improve-acute-liver-failure-in-rats-by-altering-macrophage-polarity
#2
Takanori Ito, Masatoshi Ishigami, Yoshihiro Matsushita, Marina Hirata, Kohki Matsubara, Tetsuya Ishikawa, Hideharu Hibi, Minoru Ueda, Yoshiki Hirooka, Hidemi Goto, Akihito Yamamoto
Effective treatments for acute liver failure (ALF) are still lacking. We recently reported that a single intravenous administration of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) into the D-galactosamine (D-Gal)-induced rat ALF model improves the liver injury. However, the specific factors in SHED-CM that are responsible for resolving ALF remain unclear. Here we found that depleting SHED-CM of two anti-inflammatory M2 macrophage inducers-monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (sSiglec-9)-abolished its ability to resolve rat ALF...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28267621/targeting-hepatic-macrophages-to-treat-liver-diseases
#3
REVIEW
Frank Tacke
Our view on liver macrophages in the context of health and disease has been reformed by the recognition of a remarkable heterogeneity of phagocytes in the liver. Liver macrophages consist of ontogenically distinct populations termed Kupffer cells and monocyte-derived macrophages. Kupffer cells are self-renewing, resident and principally non-migratory phagocytes, serving as sentinels for liver homeostasis. Liver injury triggers Kupffer cell activation, leading to inflammatory cytokine and chemokine release. This fosters the infiltration of monocytes into liver that give rise to large numbers of inflammatory monocyte-derived macrophages...
March 3, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28266877/glucuronidation-driving-factors-and-their-impact-on-glucuronide-disposition
#4
Guangyi Yang, Shufan Ge, Rashim Singh, Sumit Basu, Katherine Shatzer, Ming Zen, Jiong Liu, Yifan Tu, Chenning Zhang, Jinbao Wei, Jian Shi, Lijun Zhu, Zhongqiu Liu, Yuan Wang, Song Gao, Ming Hu
Glucuronidation is a well-recognized phase II metabolic pathway for a variety of chemicals including drugs and endogenous substances. Although it is usually the secondary metabolic pathway for a compound preceded by phase I hydroxylation, glucuronidation alone could serve as the dominant metabolic pathway compounds, including some with high aqueous solubility. Glucuronidation involves the metabolism of parent compound by UDP-glucuronosyltransferases (UGTs) into hydrophilic and negatively charged glucuronides that cannot exit the cell without the aid of efflux transporters...
March 7, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28249282/progress-in-the-molecular-characterization-of-hepatobiliary-transporters
#5
Dietrich Keppler
Over the last 25 years, our understanding of the driving forces for hepatobiliary elimination and knowledge of the molecular basis of uptake and efflux transport in hepatocytes have undergone fundamental changes. This refers to bile acids and many other endogenous substances as well as to drugs that are eliminated on the hepatobiliary route. In this development, not only molecular cloning, functional characterization, and localization of transporters were decisive, but also the discovery of hereditary mutations in genes encoding sinusoidal uptake transporters and canalicular export pumps in humans and rodents...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28241053/release-of-hiv-1-sequestered-in-the-vesicles-of-oral-and-genital-mucosal-epithelial-cells-by-epithelial-lymphocyte-interaction
#6
Aizezi Yasen, Rossana Herrera, Kristina Rosbe, Kathy Lien, Sharof M Tugizov
Oropharyngeal mucosal epithelia of fetuses/neonates/infants and the genital epithelia of adults play a critical role in HIV-1 mother-to-child transmission and sexual transmission of virus, respectively. To study the mechanisms of HIV-1 transmission through mucosal epithelium, we established polarized tonsil, cervical and foreskin epithelial cells. Analysis of HIV-1 transmission through epithelial cells showed that approximately 0.05% of initially inoculated virions transmigrated via epithelium. More than 90% of internalized virions were sequestered in the endosomes of epithelial cells, including multivesicular bodies (MVBs) and vacuoles...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28236326/human-es-cell-derived-hepatoblasts-are-an-optimal-lineage-stage-for-hcv-infection
#7
Fang Yan, Yi Wang, Wencheng Zhang, Mingyang Chang, Zhiying He, Jinbo Xu, Changzhen Shang, Tao Chen, Jiang Liu, Xin Wang, Xuetao Pei, Yunfang Wang
Maturation of hepatic cells can be gradually acquired through multiple stages of hepatic lineage specification, while little is known if the dynamics of HCV infection are maturationally lineage dependent. We investigated the susceptibility to HCV at multiple stages comprising human embryonic stem cells (hESCs), definitive endodermal cells (hDECs), hepatic stem cells (hHpSCs), hepatoblasts (hHBs) and mature hepatocytes (hHeps). Susceptibility to infection occurred initially at the stage of hHpSC, however, hHBs proved to have the highest permissiveness and infectivity compared with all other stages...
February 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28229142/olive-leaf-extract-concentrated-in-hydroxytyrosol-attenuates-protein-carbonylation-and-the-formation-of-advanced-glycation-end-products-in-a-hepatic-cell-line-hepg2
#8
Marta Navarro, Francisco J Morales, Sonia Ramos
Glycation takes place both at the cellular level and at the extracellular matrix level and generates, consequently, advanced glycation end-products (AGEs) associated with chronic diseases and the aging process. Two olive leaf extracts concentrated in (i) oleuropein (OLE-A; 93.9 mg oleuropein g(-1)) and (ii) hydroxytyrosol (OLE-B; 54.5 mg hydroxytyrosol g(-1)) were evaluated according to their antiglycative and antioxidant capacity in vitro. OLE-B exerted the highest anti-AGE effect in different glycation models (IC50: 0...
February 23, 2017: Food & Function
https://www.readbyqxmd.com/read/28221022/quantitative-13-c-traces-of-glucose-fate-in-hepatitis-b-virus-infected-hepatocytes
#9
Qianfen Wan, Yulan Wang, Huiru Tang
Quantitative characterization of (13)C-labeled metabolites is an important part of the stable isotope tracing method widely used in metabolic flux analysis. Given the long relaxation time and low sensitivity of (13)C nuclei, direct measurement of (13)C-labeled metabolites using one-dimensional (13)C NMR often fails to meet the demand of metabolomics studies, especially with large numbers of samples and metabolites having low abundance. Although HSQC-based 2D NMR methods have improved sensitivity with inversion detection, they are time-consuming and thus unsuitable for high-throughput absolute quantification of (13)C-labeled metabolites...
March 6, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28182770/biochemical-and-biophysical-investigations-of-the-interaction-between-human-glucokinase-and-pro-apoptotic-bad
#10
Alix Rexford, Diego A R Zorio, Brian G Miller
The glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method for the production of recombinant human BAD...
2017: PloS One
https://www.readbyqxmd.com/read/28138743/an-efficient-liquid-chromatography-high-resolution-mass-spectrometry-approach-for-the-optimization-of-the-metabolic-stability-of-therapeutic-peptides
#11
Simone Esposito, Riccardo Mele, Raffaele Ingenito, Elisabetta Bianchi, Fabio Bonelli, Edith Monteagudo, Laura Orsatti
In drug discovery, there is increasing interest in peptides as therapeutic agents due to several appealing characteristics that are typical of this class of compounds, including high target affinity, excellent selectivity, and low toxicity. However, peptides usually present also some challenging ADME (absorption, distribution, metabolism, and excretion) issues such as limited metabolic stability, poor oral bioavailability, and short half-lives. In this context, early preclinical in vitro studies such as plasma metabolic stability assays are crucial to improve developability of a peptidic drug...
January 30, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28134251/low-dose-acetaminophen-induces-early-disruption-of-cell-cell-tight-junctions-in-human-hepatic-cells-and-mouse-liver
#12
Wesam Gamal, Philipp Treskes, Kay Samuel, Gareth J Sullivan, Richard Siller, Vlastimil Srsen, Katie Morgan, Anna Bryans, Ada Kozlowska, Andreas Koulovasilopoulos, Ian Underwood, Stewart Smith, Jorge Del-Pozo, Sharon Moss, Alexandra Inés Thompson, Neil C Henderson, Peter C Hayes, John N Plevris, Pierre-Olivier Bagnaninchi, Leonard J Nelson
Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28124277/igf-1-modulates-gene-expression-of-proteins-involved-in-inflammation-cytoskeleton-and-liver-architecture
#13
V J Lara-Diaz, I Castilla-Cortazar, I Martín-Estal, M García-Magariño, G A Aguirre, J E Puche, R G de la Garza, L A Morales, U Muñoz
Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1's effects on liver by comparing wild-type controls, heterozygous igf1(+/-), and heterozygous mice treated with IGF-1 for 10 days...
January 26, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28112007/the-fatty-acid-rich-fraction-of-eruca-sativa-rocket-salad-leaf-extract-exerts-antidiabetic-effects-in-cultured-skeletal-muscle-adipocytes-and-liver-cells
#14
Mona H Hetta, Asmaa I Owis, Pierre S Haddad, Hoda M Eid
CONTEXT: Eruca sativa Mill. (Brassicaceae), commonly known as rocket salad, is a popular leafy-green vegetable with many health benefits. OBJECTIVE: To evaluate the antidiabetic activities of this plant in major insulin-responsive tissues. MATERIALS AND METHODS: Five E. sativa leaf extracts of varying polarity were prepared (aqueous extract, 70% and 95% ethanol extracts, the n-hexane-soluble fraction of the 95% ethanol extract (ES3) and the defatted 95% ethanol extract)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28105255/pi3k-ship2-pten-pathway-in-cell-polarity-and-hepatitis-c-virus-pathogenesis
#15
REVIEW
Aline Awad, Ama Gassama-Diagne
Hepatitis C virus (HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides (PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases...
January 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28066964/mechanisms-of-the-prevention-and-inhibition-of-the-progression-and-development-of-nash-by-genetic-and-pharmacological-dcr3-supplementation
#16
Pei-Chang Lee, Ling-Yu Yang, Ying-Wen Wang, Shiang-Fen Huang, Kuei-Chuan Lee, Yun-Cheng Hsieh, Ying-Ying Yang, Shie-Liang Hsieh, Ming-Chih Hou, Han-Chieh Lin, Fa-Yuah Lee, Shou-Dong Lee
AIMS: Treatment to non-alcoholic steatohepatitis (NASH) is difficult due to the absence of a proven treatment and its comprehensive mechanisms. In the NASH animal model, up-regulated hepatic inflammation and oxidative stress with the resultant M1 polarization of macrophage as well as the imbalanced adipocytokines all accelerate NASH progression. As a member of TNF receptor superfamily, decoy receptor 3 (DcR3) not only neutralizes the death ligands, but also performs immune modulations...
January 8, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28036299/v-atpase-inhibition-increases-cancer-cell-stiffness-and-blocks-membrane-related-ras-signaling-a-new-option-for-hcc-therapy
#17
Karin Bartel, Maria Winzi, Melanie Ulrich, Andreas Koeberle, Dirk Menche, Oliver Werz, Rolf Müller, Jochen Guck, Angelika M Vollmar, Karin von Schwarzenberg
Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide and the third leading cause of cancer-related death. However, therapy options are limited leaving an urgent need to develop new strategies. Currently, targeting cancer cell lipid and cholesterol metabolism is gaining interest especially regarding HCC. High cholesterol levels support proliferation, membrane-related mitogenic signaling and increase cell softness, leading to tumor progression, malignancy and invasive potential. However, effective ways to target cholesterol metabolism for cancer therapy are still missing...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28011152/adenosine-a2a-receptor-stimulation-blocks-development-of-nonalcoholic-steatohepatitis-in-mice-by-multilevel-inhibition-of-signals-that-cause-immunolipotoxicity
#18
Elisa Alchera, Simona Rolla, Chiara Imarisio, Valentina Bardina, Guido Valente, Francesco Novelli, Rita Carini
Lipotoxicity and immunoinflammation are associated with the evolution of steatosis toward nonalcoholic steatohepatitis (NASH). This study reports the ability of adenosine A2a receptor (A2aR) activation to inhibit NASH development by modulating the responses of CD4(+) T-helper (Th) cells to avoid an immuno-mediated potentiation of lipotoxicity. The effect of the A2aR agonist CGS21680 on immunoinflammatory signals, CD4(+)Th cell infiltration and immunolipotoxicity was analyzed in steatotic C57BL/6 mice fed with a methionine-choline-deficient (MCD) diet and in mouse hepatocytes exposed to palmitic acid (PA)...
December 6, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27923925/biliary-secretion-of-quasi-enveloped-human-hepatitis-a-virus
#19
Asuka Hirai-Yuki, Lucinda Hensley, Jason K Whitmire, Stanley M Lemon
Hepatitis A virus (HAV) is an unusual picornavirus that is released from cells cloaked in host-derived membranes. These quasi-enveloped virions (eHAV) are the only particle type circulating in blood during infection, whereas only nonenveloped virions are shed in feces. The reason for this is uncertain. Hepatocytes, the only cell type known to support HAV replication in vivo, are highly polarized epithelial cells with basolateral membranes facing onto hepatic (blood) sinusoids and apical membranes abutting biliary canaliculi from which bile is secreted to the gut...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27916608/functional-properties-of-hepatocytes-in-vitro-are-correlated-with-cell-polarity-maintenance
#20
Anja Zeigerer, Anne Wuttke, Giovanni Marsico, Sarah Seifert, Yannis Kalaidzidis, Marino Zerial
Exploring the cell biology of hepatocytes in vitro could be a powerful strategy to dissect the molecular mechanisms underlying the structure and function of the liver in vivo. However, this approach relies on appropriate in vitro cell culture systems that can recapitulate the cell biological and metabolic features of the hepatocytes in the liver whilst being accessible to experimental manipulations. Here, we adapted protocols for high-resolution fluorescence microscopy and quantitative image analysis to compare two primary hepatocyte culture systems, monolayer and collagen sandwich, with respect to the distribution of two distinct populations of early endosomes (APPL1 and EEA1-positive), endocytic capacity, metabolic and signaling activities...
January 1, 2017: Experimental Cell Research
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