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https://www.readbyqxmd.com/read/29761173/liver-enriched-transcription-factor-expression-relates-to-chronic-hepatic-failure-in-humans
#1
Jorge Guzman-Lepe, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Yang Wang, Wendy M Mars, Yoshinao Oda, Yuki Bekki, Masahiro Shimokawa, Huanlin Wang, Tomoharu Yoshizumi, Yoshihiko Maehara, Aaron Bell, Ira J Fox, Kazuki Takeishi, Alejandro Soto-Gutierrez
The mechanisms by which the liver fails in end-stage liver disease remain elusive. Disruption of the transcription factor network in hepatocytes has been suggested to mediate terminal liver failure in animals. However, this hypothesis remains unexplored in human subjects. To study the relevance of transcription factor expression in terminal stages of chronic liver failure in humans, we analyzed the expression of liver-enriched transcription factors (LETFs) hepatocyte nuclear factor (HNF)4α, HNF1α, forkhead box protein A2 (FOXA2), CCAAT/enhancer-binding protein (CEBP)α, and CEBPβ...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29752404/low-density-lipoprotein-receptor-related-protein-1-dysfunction-synergizes-with-dietary-cholesterol-to-accelerate-steatohepatitis-progression
#2
Allyson N Hamlin, Sivaprakasam Chinnarasu, Yinyuan Ding, Xunde Xian, Joachim Herz, Anja Jaeschke, David Y Hui
Reduced low density lipoprotein receptor-related protein-1 (LRP1) expression in the liver is associated with poor prognosis of liver cirrhosis and hepatocellular carcinoma.  Previous studies have shown that hepatic LRP1 deficiency exacerbates palmitate-induced steatosis and toxicity in vitro and also promotes high fat diet-induced hepatic insulin resistance and hepatic steatosis in vivo   The current study examined the impact of liver-specific LRP1 deficiency in disease progression to steatohepatitis.  hLrp1+/+ mice with normal LRP1 expression and hLrp1-/- mice with hepatocyte-specific LRP1 inactivation were fed a high fat-high cholesterol (HFHC) diet for 16 weeks...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29750835/lrp1-suppresses-bone-resorption-in-mice-by-inhibiting-the-rankl-stimulated-nf%C3%AE%C2%BAb-and-p38-pathways-during-osteoclastogenesis
#3
Di Lu, Jianshuang Li, Huadie Liu, Gabrielle E Foxa, Kevin Weaver, Jie Li, Bart O Williams, Tao Yang
Single nucleotide polymorphisms in the LRP1 gene coding sequence are associated with low bone mass, and cell culture studies suggest that LRP1 plays a role in osteoblast proliferation and osteoblast-mediated osteoclastogenesis. However, the in vivo function of LRP1 in bone homeostasis has not been explored. In this work, we studied the osteoclast-specific role of LRP1 in bone homeostasis using a Ctsk-Cre;Lrp1f/f mouse model on the C57BL/6J background. These mice had a dramatically decreased trabecular bone mass with markedly more osteoclasts, while the osteoblast activity was unaffected or slightly increased...
May 11, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29749311/role-of-the-ldl-receptor-related-protein-1-in-regulating-protease-activity-and-signaling-pathways-in-the-vasculature
#4
Dianaly T Au, Allison L Arai, William E Fondrie, Selen C Muratoglu, Dudley K Strickland
Aortic aneurysms represent a significant clinical problem as they largely go undetected until a rupture occurs. Currently, an understanding of mechanisms leading to aneurysm formation is limited. Numerous studies clearly indicate that vascular smooth muscle cells play a major role in the development and response of the vasculature to hemodynamic changes and defects in these responses can lead to aneurysm formation. The LDL receptor-related protein 1 (LRP1) is major smooth muscle cell receptor that has the capacity to mediate the endocytosis of numerous ligands and to initiate and regulate signaling pathways...
May 11, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29744695/bovine-lactoferrin-promotes-energy-expenditure-via-the-camp-pka-signaling-pathway-in-human-reprogrammed-brown-adipocytes
#5
Kanae Nakamura, Tsunao Kishida, Akika Ejima, Riho Tateyama, Satoru Morishita, Tomoji Ono, Michiaki Murakoshi, Keikichi Sugiyama, Hoyoku Nishino, Osam Mazda
Lactoferrin (LF) is a multifunctional protein in mammalian milk. We previously reported that enteric-coated bovine LF reduced the visceral fat in a double-blind clinical study. We further demonstrated that bovine LF (bLF) inhibited adipogenesis and promoted lipolysis in white adipocytes, but the effect of bLF on brown adipocytes has not been clarified. In this study, we investigated the effects of bLF on energy expenditure and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway using human reprogrammed brown adipocytes generated by gene transduction...
May 9, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29720671/genetic-variation-in-117-myelination-related-genes-in-schizophrenia-replication-of-association-to-lipid-biosynthesis-genes
#6
Tomasz Stokowy, Tatiana Polushina, Ida E Sønderby, Robert Karlsson, Sudheer Giddaluru, Stephanie Le Hellard, Sarah E Bergen, Patrick F Sullivan, Ole A Andreassen, Srdjan Djurovic, Christina M Hultman, Vidar M Steen
Schizophrenia is a serious psychotic disorder with high heritability. Several common genetic variants, rare copy number variants and ultra-rare gene-disrupting mutations have been linked to disease susceptibility, but there is still a large gap between the estimated and explained heritability. Since several studies have indicated brain myelination abnormalities in schizophrenia, we aimed to examine whether variants in myelination-related genes could be associated with risk for schizophrenia. We established a set of 117 myelination genes by database searches and manual curation...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29700775/somatostatin-maintains-permeability-and-integrity-of-blood-brain-barrier-in-%C3%AE-amyloid-induced-toxicity
#7
Seungil Paik, Rishi K Somvanshi, Ujendra Kumar
In Alzheimer's disease (AD), the impaired clearance of β-amyloid peptide (Aβ) due to disrupted tight junction and transporter proteins is the prominent cause of disease progression. Somatostatin (SST) blocks the aggregation of Aβ and inflammation whereas reduction of SST levels in the CSF and brain tissue is associated with impaired cognitive function and memory loss. However, the role of SST in preservation of blood-brain barrier (BBB) integrity and functionality in Aβ-induced toxicity is not known. In the present study using human CMEC/D3 cells, we demonstrate that SST prevents Aβ-induced BBB permeability by regulating LRP1 and RAGE expression and improving the disrupted tight junction proteins...
April 26, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29679668/a-novel-peptide-ligand-rap12-of-lrp1-for-glioma-targeted-drug-delivery
#8
Huitong Ruan, Zhilan Chai, Qing Shen, Xishan Chen, Bingxia Su, Cao Xie, Changyou Zhan, Shengyu Yao, Huan Wang, Mingfei Zhang, Man Ying, Weiyue Lu
The receptor associated protein (RAP) is a 39 kDa chaperone protein, binding tightly to low-density lipoprotein receptor-related protein-1 (LRP1) that is overexpressed in glioma, tumor neovasculature, vasculogenic mimicry (VM), the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). Herein, we miniaturized the RAP protein into a short peptide RAP12 (EAKIEKHNHYQK) aiding by computer-aided peptide design technique. RAP12 contained the essential lysines at the positions 253 and 256. The binding affinity of RAP12 to LRP1 was theoretically and experimentally evaluated...
April 18, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29674277/long-noncoding-rna-foxd2-as1-accelerates-the-gemcitabine-resistance-of-bladder-cancer-by-sponging-mir-143
#9
Qing An, Liyang Zhou, Nan Xu
Increasing evidences have proved that long noncoding RNAs (lncRNAs) modulate the tumorigenesis of bladder cancer involved in multiple pathophysiological processes. In the study, we investigate the role of lncRNA FOXD2-AS1 in the gemcitabine (GEM) resistant bladder cancer and explore its potential mechanism. Results showed that lncRNA FOXD2-AS1 was high-expressed in gemcitabine-resistant bladder cancer cells. In vitro experiments, FOXD2-AS1 knockdown suppressed the 50% inhibitive concentration (IC50) of gemcitabine, drug-resistance related genes (MDR1, MRP2, LRP1) expression, invasion and ABCC3 protein expression in gemcitabine-resistant bladder cancer cells (T24/GEM, 5637/GEM)...
April 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29669912/insulin-induced-exocytosis-regulates-the-cell-surface-level-of-low-density-lipoprotein-related-protein-1-in-m%C3%A3-ller-glial-cells
#10
Virginia Actis Dato, Rubén A Grosso, María C Sánchez, Claudio M Fader, Gustavo A Chiabrando
Low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) is expressed in retinal Müller glial cells (MGCs) and regulates intracellular translocation to the plasma membrane (PM) of the membrane proteins involved in cellular motility and activity. Different functions of MGCs may be influenced by insulin, including the removal of extracellular glutamate in the retina. In the present work, we investigated whether insulin promotes LRP1 translocation to the PM in the Müller glial-derived cell line MIO-M1...
April 18, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29644529/effects-of-increased-accumulation-of-doxorubicin-due-to-emodin-on-efflux-transporter-and-lrp1-expression-in-lung-adenocarcinoma-and-colorectal-carcinoma-cells
#11
Vidhya V Iyer, P Yoga Priya, Jeipreeti Kangeyavelu
Treatment with doxorubicin (dox) and emodin, separately and together, under normoxic and hypoxia-like conditions induced by CoCl2 , led to greater intracellular compound accumulation over 10 h post-addition in the presence of CoCl2 in lung adenocarcinoma (A549) and colorectal carcinoma (HCT-15) cell lines. Confocal microscopy revealed that emodin, by itself, showed high cytosolic distribution in both cell lines, at 40 min post-addition but had entered the nuclei by 2 h, while dox entered the nuclei by 40 min...
April 11, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29622560/role-of-adamts-a-disintegrin-and-metalloproteinase-with-thrombospondin-motifs-5-in-aortic-dilatation-and-extracellular-matrix-remodeling
#12
Marika Fava, Javier Barallobre-Barreiro, Ursula Mayr, Ruifang Lu, Athanasios Didangelos, Ferheen Baig, Marc Lynch, Norman Catibog, Abhishek Joshi, Temo Barwari, Xiaoke Yin, Marjan Jahangiri, Manuel Mayr
OBJECTIVE: Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix). The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation. This study aimed to investigate the contribution of ADAMTS-5 to TAA development. APPROACH AND RESULTS: A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat )...
April 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29617432/vitamin-k2-improves-proliferation-and-migration-of-bovine-skeletal-muscle-cells-in-vitro
#13
Sissel Beate Rønning, Mona Elisabeth Pedersen, Ragnhild Stenberg Berg, Bente Kirkhus, Rune Rødbotten
Skeletal muscle function is highly dependent on the ability to regenerate, however, during ageing or disease, the proliferative capacity is reduced, leading to loss of muscle function. We have previously demonstrated the presence of vitamin K2 in bovine skeletal muscles, but whether vitamin K has a role in muscle regulation and function is unknown. In this study, we used primary bovine skeletal muscle cells, cultured in monolayers in vitro, to assess a potential effect of vitamin K2 (MK-4) during myogenesis of muscle cells...
2018: PloS One
https://www.readbyqxmd.com/read/29610366/exomechip-analyses-identify-genes-affecting-mortality-after-hla-matched-unrelated-donor-blood-and-marrow-transplantation
#14
Qianqian Zhu, Li Yan, Qian Liu, Chi Zhang, Lei Wei, Qiang Hu, Leah Preus, Alyssa I Clay-Gilmour, Kenan Onel, Daniel O Stram, Loreall Pooler, Xin Sheng, Christopher A Haiman, Xiaochun Zhu, Stephen R Spellman, Marcelo Pasquini, Philip L McCarthy, Song Liu, Theresa Hahn, Lara E Sucheston-Campbell
While survival outcomes have significantly improved, up to 40% of patients die within 1-year after HLA-matched unrelated donor (URD) blood and marrow transplant (BMT). To identify non-HLA genetic contributors to mortality after BMT, we performed the first exome-wide association study in the DISCOVeRY-BMT cohorts using the Illumina HumanExome BeadChip. This study includes 2,473 AML, ALL, MDS patients and 2,221 10/10 HLA matched donors treated from 2000-2011. Single variant and gene-level analyses were performed with overall survival (OS), transplant-related mortality (TRM), and disease-related mortality (DRM)...
April 2, 2018: Blood
https://www.readbyqxmd.com/read/29602203/lncrna-nr2f1-as1-regulates-hepatocellular-carcinoma-oxaliplatin-resistance-by-targeting-abcc1-via-mir-363
#15
Hai Huang, Jie Chen, Cheng-Ming Ding, Xin Jin, Ze-Ming Jia, Jian Peng
Emerging evidence has validated the vital role of long non-coding RNA (lncRNA) in the chemoresistance of cancer treatment. In the present study, we investigate the function of lncRNA NR2F1-AS1 on oxaliplatin (OXA) resistance of hepatocellular carcinoma (HCC) and discover the underlying molecular mechanism. Results revealed that lncRNA NR2F1-AS1 was up-regulated in oxaliplatin-resistant HCC tissue and cells using microarray analysis and RT-PCR. Meanwhile, ABCC1 protein was overexpressed in OXA-resistant HCC cells (Huh7/OXA and HepG2/OXA)...
March 30, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29596966/characterization-of-hit-compounds-identified-from-high-throughput-screening-for-their-effect-on-blood-brain-barrier-integrity-and-amyloid-%C3%AE-clearance-in-vitro-and-in-vivo-studies
#16
Khaled H Elfakhri, Quoc-Viet Duong, Courtney Langley, Ashley Depaula, Youssef M Mousa, Trista Lebeouf, Courtney Cain, Amal Kaddoumi
In Alzheimer's disease (AD) the blood-brain barrier (BBB) is compromised, thus therapeutic targeting of the BBB to enhance its integrity and function could be a unique approach to treat, slow or hold the progression of AD. Recently, we have developed an in vitro high-throughput screening assay to screen for compounds that increase the integrity of a cell-based BBB model. Results from primary screen identified multiple hit compounds that enhanced the monolayer integrity. Herein, further characterization of selected hit compounds, namely 8-bromoguanosine cyclic monophosphate, JW74, 1,10-phenanthroline monohydrate, SB216763 and α-tocopherol was performed...
March 26, 2018: Neuroscience
https://www.readbyqxmd.com/read/29559555/site-specific-o-glycosylation-of-members-of-the-low-density-lipoprotein-receptor-superfamily-enhances-ligand-interactions
#17
Shengjun Wang, Yang Mao, Yoshiki Narimatsu, Zilu Ye, Weihua Tian, Christoffer K Goth, Erandi Lira-Navarrete, Nis Borbye Pedersen, Asier Benito-Vicente, Cesar Martin, Kepa B Uribe, Ramon Hurtado-Guerrero, Christina Christoffersen, Nabil G Seidah, Rikke Nielsen, Erik I Christensen, Lars Hansen, Eric P Bennett, Sergey Y Vakhrushev, Katrine T Schjoldager, Henrik Clausen
The low-density lipoprotein receptor (LDLR) and related proteins are important for the transport of diverse biomolecules across cell membranes and barriers. Their functions are especially relevant for cholesterol homeostasis and diseases, including neurodegenerative and kidney disorders. Members of the LDLR-related protein family share LDLR class A (LA) repeats providing binding properties for lipoproteins and other biomolecules. We previously demonstrated that short linker regions between these LA repeats contain conserved O-glycan-sites...
March 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29558961/apolipoprotein-e-isoform-dependently-affects-tat-mediated-hiv-1-ltr-transactivation
#18
Nabab Khan, Gaurav Datta, Jonathan D Geiger, Xuesong Chen
BACKGROUND: Apolipoprotein E (ApoE) is the major carrier protein that mediates the transport and delivery of cholesterol and other lipids in the brain. Three isoforms of ApoE (ApoE2, ApoE3, ApoE4) exist in humans, and their relative expression levels impact HIV-1 infection, HIV-1/AIDS disease progression, and cognitive decline associated with HIV-1-associated neurocognitive disorder. Because HIV-1 Tat, a viral protein essential for HIV-1 replication, can bind to low-density lipoprotein receptor-related protein 1 (LRP1) that controls ApoE uptake in the brain, we determined the extent to which different isoforms of ApoE affected Tat-mediated HIV-1 LTR transactivation...
March 20, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29550924/role-of-lactoferrin-and-its-receptors-on-biliary-epithelium
#19
Romina Mancinelli, Francesca Olivero, Guido Carpino, Diletta Overi, Luigi Rosa, Maria Stefania Lepanto, Antimo Cutone, Antonio Franchitto, Gianfranco Alpini, Paolo Onori, Piera Valenti, Eugenio Gaudio
Human lactoferrin is an iron-binding glycoprotein present at high concentrations in breast milk and colostrum. It is produced by many exocrine glands and widely distributed in a variety of body fluids. This protein has antimicrobial, immunomodulatory, antioxidant, and anticancer properties. Two important hLf receptors have been identified: LDL receptor related protein (LRP1), a low specificity receptor, and intelectin-1 (ITLN1), a high specificity receptor. No data are present on the role of hLf on the biliary epithelium...
March 17, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29547901/molecular-partners-of-hnot-alg3-the-human-counterpart-of-the-drosophila-not-and-yeast-alg3-gene-suggest-its-involvement-in-distinct-cellular-processes-relevant-to-congenital-disorders-of-glycosylation-cancer-neurodegeneration-and-a-variety-of-further-pathologies
#20
Benedikt Hacker, Christoph Schultheiß, Michael Döring, Ursula Kurzik-Dumke
This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila Neighbour of TID and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1...
June 1, 2018: Human Molecular Genetics
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