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Hepatocyte polarity

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https://www.readbyqxmd.com/read/28519899/hepatic-aa-amyloidosis-in-a-cat-cytologic-and-histologic-identification-of-aa-amyloid-in-macrophages
#1
Sakurako Neo-Suzuki, Takayuki Mineshige, Junichi Kamiie, Hideki Kayanuma, Yukako Mochizuki, Masaharu Hisasue, Ryo Tsuchiya, Kinji Shirota
A 3-year-old, spayed female, Domestic Shorthair cat presented with anorexia, lethargy, vomiting, probable hemoabdomen, and multiple masses on the right lateral liver lobe. Clinicopathologic and imaging abnormalities included anemia, azotemia, icterus, and hepatomegaly with hypoechoic masses. On cytologic evaluation of a fine-needle aspiration of a liver mass there was abundant extracellular pink- to purple-colored material between hepatocytes. The amorphous material was stained with direct fast scarlet (DFS), and green birefringent areas were observed under polarized light, confirming the presence of amyloid...
May 18, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28500084/bisphenol-a-promotes-hepatic-lipid-deposition-involving-kupffer-cell-m1-polarization-in-male-mice
#2
Qiong Lv, Rufei Gao, Chuan Peng, Juan Yi, Lulu Liu, Shumin Yang, Danting Li, Jinbo Hu, Ting Luo, Mei Mei, Ying Song, Chaodong Wu, Xiaoqiu Xiao, Qifu Li
Bisphenol A (BPA), as one of the most common environmental endocrine disruptors, is considered to promote hepatic lipid deposition, but the mechanisms has not been fully elucidated. The polarization of Kupffer cells (KCs) plays an important role in hepatic inflammation by promoting pro-inflammatory M1 phenotype (M1KCs), which contributes to dysregulated lipid metabolism. The purpose of this study is to investigate the role of KC polarization in BPA-induced hepatosteatosis in male mice. In this study, we examined hepatic lipid contents and quantified M1KC in BPA-treated CD1 mice, and further explored the interaction between KCs and hepatocytes by using conditional HepG2 cell culture...
May 12, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28437613/evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#3
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
The role of bile salt export protein (BSEP) inhibition in drug-induced liver injury (DILI) has been investigated widely, while inhibition of the canalicular multidrug resistant protein 3 (MDR3) has received less attention. This transporter plays a pivotal role in secretion of phospholipids into bile and functions coordinately with BSEP to mediate the formation of bile acid-containing biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined across 125 drugs (70 of Most-DILI-concern and 55 of No-DILI-concern)...
May 4, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28333715/noninvasive-imaging-of-stored-red-blood-cell-transfusion-aggravating-sepsis-induced-liver-injury-associated-with-increased-activation-of-m1-polarized-kupffer-cells
#4
Tao Wu, Lei Wang, Jie An, Chao Y Wu, Yue Wang, Lu Qian, Jun Zhou, Yu L Zhang, Qian Q Zhou, Xiao H Wang, Hua F Wang, Qiu X Fu, Lin S Zhan
Liver injury has a critical effect on the severity and outcome of sepsis. The impact of stored RBCs on the pathogenesis of sepsis-associated hepatic injury is not well understood. Therefore, to investigate the effects of stored-RBC transfusion on sepsis-induced liver damage as well as the associated mechanism, we constructed a sepsis mouse model enabling non-invasive imaging of bacterial infection caused by Pseudomonas aeruginosa, a common gram-negative respiratory pathogen. We showed that transfusions with stored RBCs enhanced sepsis-induced liver injury in vivo, and liver injury exacerbated the severity of sepsis and decreased survival in P...
March 22, 2017: Shock
https://www.readbyqxmd.com/read/28330995/hepatic-fcrn-regulates-albumin-homeostasis-and-susceptibility-to-liver-injury
#5
Michal Pyzik, Timo Rath, Timothy T Kuo, Sanda Win, Kristi Baker, Jonathan J Hubbard, Rosa Grenha, Amit Gandhi, Thomas D Krämer, Adam R Mezo, Zachary S Taylor, Kevin McDonnell, Vicki Nienaber, Jan Terje Andersen, Atsushi Mizoguchi, Laurence Blumberg, Shalaka Purohit, Susan D Jones, Greg Christianson, Wayne I Lencer, Inger Sandlie, Neil Kaplowitz, Derry C Roopenian, Richard S Blumberg
The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28323124/cd44-is-a-key-player-in-non-alcoholic-steatohepatitis
#6
Stéphanie Patouraux, Déborah Rousseau, Stéphanie Bonnafous, Cynthia Lebeaupin, Carmelo Luci, Clémence M Canivet, Anne-Sophie Schneck, Adeline Bertola, Marie-Christine Saint-Paul, Antonio Iannelli, Jean Gugenheim, Rodolphe Anty, Albert Tran, Béatrice Bailly-Maitre, Philippe Gual
BACKGROUND & AIMS: Cluster of differentiation (CD)44 regulates adipose tissue inflammation in obesity and hepatic leukocyte recruitment in a lithogenic context. However, its role in hepatic inflammation in a mouse model of steatohepatitis and its relevance in humans have not yet been investigated. We aimed to evaluated the contribution of CD44 to non-alcoholic steatohepatitis (NASH) development and liver injury in mouse models and in patients at various stages of non-alcoholic fatty liver disease (NAFLD) progression...
March 16, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28272754/hyperpolarized-%C3%AE-1-13-c-gluconolactone-as-a-probe-of-the-pentose-phosphate-pathway
#7
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
#8
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
#9
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 the liver, which give rise to large numbers of inflammatory monocyte-derived macrophages...
March 4, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28266877/glucuronidation-driving-factors-and-their-impact-on-glucuronide-disposition
#10
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
#11
REVIEW
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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...
April 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
#18
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
#19
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...
May 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
#20
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
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