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Hepatocyte polarity

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https://www.readbyqxmd.com/read/28182770/biochemical-and-biophysical-investigations-of-the-interaction-between-human-glucokinase-and-pro-apoptotic-bad
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
December 28, 2016: 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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27909560/induction-of-heme-oxygenase-1-with-dietary-quercetin-reduces-obesity-induced-hepatic-inflammation-through-macrophage-phenotype-switching
#12
Chu-Sook Kim, Hye-Seon Choi, Yeonsoo Joe, Hun Taeg Chung, Rina Yu
BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype...
December 2016: Nutrition Research and Practice
https://www.readbyqxmd.com/read/27903585/autophagy-in-chronic-liver-diseases-the-two-faces-of-janus
#13
Philippe Gual, Helene Gilgenkrantz, Sophie Lotersztajn
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis, steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (Macroautophagy and Chaperome-mediated autophagy) and chronic liver diseases have been reported...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27853646/hepatocellular-carcinoma-is-accelerated-by-nash-involving-m2-macrophage-polarization-mediated-by-hif-1%C3%AE-induced-il-10
#14
Aditya Ambade, Abhishek Satishchandran, Banishree Saha, Benedek Gyongyosi, Patrick Lowe, Karen Kodys, Donna Catalano, Gyongyi Szabo
Obesity-related inflammation promotes cancer development. Tissue resident macrophages affect tumor progression and the tumor micro-environment favors polarization into alternatively activated macrophages (M2) that facilitate tumor invasiveness. Here, we dissected the role of western diet-induced NASH in inducing macrophage polarization in a carcinogen initiated model of hepatocellular carcinoma (HCC). Adult C57BL/6 male mice received diethyl nitrosamine (DEN) followed by 24 weeks of high fat-high cholesterol-high sugar diet (HF-HC-HSD)...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27818736/combined-toxic-effects-of-polar-and-nonpolar-chemicals-on-human-hepatocytes-hepg2-cells-by-quantitative-property-activity-relationship-modeling
#15
Ki-Woong Kim, Yong Lim Won, Dong Jin Park, Young Sun Kim, Eun Sil Jin, Sung Kwang Lee
We determined the toxicity of mixtures of ethyl acetate (EA), isopropyl alcohol (IPA), methyl ethyl ketone (MEK), toluene (TOL) and xylene (XYL) with half-maximal effective concentration (EC50) values obtained using human hepatocytes cells. According to these data, quantitative property-activity relationships (QPAR) models were successfully proposed to predict the toxicity of mixtures by multiple linear regressions (MLR). The leave-one-out cross validation method was used to find the best subsets of descriptors in the learning methods...
October 2016: Toxicological Research
https://www.readbyqxmd.com/read/27792760/ampk-activation-prevents-and-reverses-drug-induced-mitochondrial-and-hepatocyte-injury-by-promoting-mitochondrial-fusion-and-function
#16
Sun Woo Sophie Kang, Ghada Haydar, Caitlin Taniane, Geoffrey Farrell, Irwin M Arias, Jennifer Lippincott-Schwartz, Dong Fu
Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria...
2016: PloS One
https://www.readbyqxmd.com/read/27722715/a-vertical-flow-bioreactor-array-compacts-hepatocytes-for-enhanced-polarity-and-functions
#17
Liang Zhu, Huanming Xia, Zhenfeng Wang, Eliza Li Shan Fong, Junjun Fan, Wen Hao Tong, Yen Peng Daphne Seah, Weian Zhang, Qiushi Li, Hanry Yu
Although hepatocytes in vivo experience intra-abdominal pressure (IAP), pressure is typically not incorporated in hepatocyte culture systems. The cuboidal cell shape and extent of intercellular contact between cultured hepatocytes are critical parameters that influence the differentiated hepatic phenotype. Using a microfluidic device, the application of pressure to artificially compact cells and forge cell-cell interactions was previously demonstrated to be effective in accelerating hepatic repolarization. In seeking to implement this approach to higher throughput culture platforms for potential drug screening applications, we specifically designed a vertical-flow compaction bioreactor array (VCBA) that compacts hepatocytes within the range of IAP and portal pressure in vivo in a multi-well setup...
October 5, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27643636/fabrication-of-3d-culture-platform-with-sandwich-architecture-for-preserving-liver-specific-functions-of-hepatocytes-using-3d-bioprinter
#18
Kenichi Arai, Toshiko Yoshida, Motonori Okabe, Mitsuaki Goto, Tanveer Ahmad Mir, Chika Soko, Yoshinari Tsukamoto, Toshihiro Akaike, Toshio Nikaido, Kaixuan Zhou, Makoto Nakamura
The development of new three-dimensional (3D) cell culture system that maintains the physiologically relevant signals of hepatocytes is essential in drug discovery and tissue engineering research. Conventional two-dimensional (2D) culture yields cell growth, proliferation and differentiation. However, gene expression and signaling profiles can be different from in vivo environment. Here, we report the fabrication of a 3D culture system using an artificial scaffold and our custom-made inkjet 3D-bioprinter as a new strategy for studying liver-specific functions of hepatocytes...
September 19, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27642075/liver-serine-palmitoyltransferase-activity-deficiency-in-early-life-impairs-adherens-junctions-and-promotes-tumorigenesis
#19
Zhiqiang Li, Inamul Kabir, Hui Jiang, Hongwen Zhou, Jenny Libien, Jianying Zeng, Albert Stanek, Peiqi Ou, Kailyn R Li, Shane Zhang, Hai H Bui, Ming-Shang Kuo, Tae-Sik Park, Benjamin Kim, Tilla S Worgall, Chongmin Huan, Xian-Cheng Jiang
: Serine palmitoyltransferase is the key enzyme in sphingolipid biosynthesis. Mice lacking serine palmitoyltransferase are embryonic lethal. We prepared liver-specific mice deficient in the serine palmitoyltransferase long chain base subunit 2 gene using an albumin-cyclization recombination approach and found that the deficient mice have severe jaundice. Moreover, the deficiency impairs hepatocyte polarity, attenuates liver regeneration after hepatectomy, and promotes tumorigenesis. Importantly, we show that the deficiency significantly reduces sphingomyelin but not other sphingolipids in hepatocyte plasma membrane; greatly reduces cadherin, the major protein in adherens junctions, on the membrane; and greatly induces cadherin phosphorylation, an indication of its degradation...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27626926/differential-lipotoxic-effects-of-palmitate-and-oleate-in-activated-human-hepatic-stellate-cells-and-epithelial-hepatoma-cells
#20
Alexandra M Hetherington, Cynthia G Sawyez, Emma Zilberman, Alexandra M Stoianov, Debra L Robson, Nica M Borradaile
BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) progression to fibrosis, cirrhosis and hepatocellular carcinoma, alters the cellular composition of this organ. During late-stage NAFLD, fibrotic and possibly cancerous cells can proliferate and, like normal hepatocytes, are exposed to high concentrations of fatty acids from both surrounding tissue and circulating lipid sources. We hypothesized that primary human activated hepatic stellate cells and epithelial hepatoma (HepG2) cells respond differently to lipotoxic conditions, and investigated the mechanisms involved...
2016: Cellular Physiology and Biochemistry
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