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Low density lipoprotein receptor related protein 1

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https://www.readbyqxmd.com/read/29312635/lrp6-promotes-invasion-and-metastasis-of-colorectal-cancer-through-cytoskeleton-dynamics
#1
Qian Yao, Yu An, Wei Hou, Ya-Nan Cao, Meng-Fei Yao, Ning-Ning Ma, Lin Hou, Hong Zhang, Hai-Jing Liu, Bo Zhang
Low density lipoprotein (LDL) receptor-related protein-6 (LRP6) is an important co-receptor of Wnt pathway, which plays a predominant role in development and progression of colorectal cancer. Recently, dysregulation of LRP6 has proved to be involved in the progression of cancers, but its biological role and clinical significance in colorectal cancer remain unclear. In present study, we revealed that phosphorylation of LRP6 was aberrantly upregulated in colorectal carcinoma correlating with TNM or Dukes staging and worse prognosis...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29303184/the-combination-of-endolysosomal-escape-and-basolateral-stimulation-to-overcome-the-difficulties-of-easy-uptake-hard-transcytosis-of-ligand-modified-nanoparticles-in-oral-drug-delivery
#2
Yi Cui, Wei Shan, Rui Zhou, Min Liu, Lei Wu, Quan Guo, Yaxian Zheng, Jiawei Wu, Yuan Huang
Ligand-modified nanoparticles (NPs) are an effective tool to increase the endocytosis efficiency of drugs, but these functionalized NPs face the drawback of "easy uptake hard transcytosis" in the oral delivery of proteins and peptides. Adversely, the resulting deficiency in transcytosis has not attracted much attention. Herein, NPs modified with the low-density lipoprotein receptor (LDLR) ligand NH2-C6-[cMPRLRGC]c-NH2, i.e., peptide-22 (P22NPs) were fabricated to investigate strategies related to the enhancement of transcytosis...
January 5, 2018: Nanoscale
https://www.readbyqxmd.com/read/29299920/targeted-imaging-of-brain-tumors-with-a-framework-nucleic-acid-probe
#3
Tian Tian, Jiang Li, Cao Xie, Yanhong Sun, Haozhi Lei, Xinyi Liu, Jiaoyun Xia, Jiye Shi, Lihua Wang, Weiyue Lu, Chunhai Fan
Development of agents for delivering drugs and imaging probes across the blood brain barrier (BBB) remains a major challenge. In this study, we designed a biocompatible framework nucleic acid (FNA)-based imaging probe for brain tumor targeting. We employed a typical type of FNAs, tetrahedral DNA nanostructures (TDNs), as the building block, which were modified with angiopep-2 (ANG), a 19-mer peptide derived from human Kunitz domain of aprotinin. This probe exhibited high binding efficiency with low-density lipoprotein receptor-related protein-1 (LRP-1) of BBB and glioma...
January 4, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29295851/proteomic-profiling-for-cardiovascular-biomarker-discovery-in-orthostatic-hypotension
#4
Madeleine Johansson, Fabrizio Ricci, Nay Aung, Richard Sutton, Olle Melander, Artur Fedorowski
Orthostatic hypotension (OH) has been linked with higher incidence of cardiovascular disease, but little is known about the mechanisms behind this association. We aimed to identify cardiovascular disease biomarkers associated with OH through a proteomic profiling approach. Seven hundred seventy-eight patients with unexplained syncope or orthostatic intolerance underwent head-up tilt test and supine blood samples. Of these, 220 met diagnostic criteria of OH, and 179 demonstrated normal hemodynamic response during head-up tilt test...
January 2, 2018: Hypertension
https://www.readbyqxmd.com/read/29285097/mir-34a-and-mir-125b-are-upregulated-in-peripheral-blood-mononuclear-cells-from-patients-with-type-2-diabetes-mellitus
#5
Yanxin Shen, Huiling Xu, Xiaoyuan Pan, Weijiang Wu, Hui Wang, Linlin Yan, Miaomiao Zhang, Xia Liu, Sheng Xia, Qixiang Shao
Type 2 diabetes mellitus (T2DM) is a leading cause of blindness, non-traumatic amputation and end-stage renal disease, as well as a major cardiovascular risk factor. To determine whether miR-125b and miR-34a serve an important role in the development of T2DM, the current study investigated the expression profile of two microRNAs (miR-34a and miR-125b) and their relative genes in peripheral blood mononuclear cells from 73 patients with T2DM and 52 healthy donors by reverse transcription-quantitative polymerase chain reaction In addition, the association between miR-34a, miR-125b and their relevant genes expression profile were analyzed with respect to the pathogenesis of T2DM...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29285052/suppression-of-alzheimer-s-disease-related-phenotypes-by-the-heat-shock-protein-70-inducer-geranylgeranylacetone-in-app-ps1-transgenic-mice-via-the-erk-p38-mapk-signaling-pathway
#6
Yuan Sun, Jiang-Rong Zhang, Shuyan Chen
HSP70 overexpression has a remedying effect in neurodegenerative diseases. In Alzheimer's disease (AD), the suppressive effects of HSP70 overexpression on AD-related phenotypes and the underlying mechanisms are unknown. In the current study, the effect of geranylgeranylacetone (GGA), a non-toxic inducer of heat shock protein (HSP)-70 expression, on cognitive function and other pathological phenotypes were evaluated in APP/PS1 mice. It was observed that all doses of orally administered GGA (200, 400, and 800 mg/kg/day) improved cognitive deficit (P<0...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29262309/lrp1-a-chameleon-receptor-of-lung-inflammation-and-repair
#7
REVIEW
Lukasz Wujak, Jennifer Schnieder, Liliana Schaefer, Malgorzata Wygrecka
The lung displays a remarkable capability to regenerate following injury. Considerable effort has been made thus far to understand the cardinal processes underpinning inflammation and reconstruction of lung tissue. However, the factors determining the resolution or persistence of inflammation and efficient wound healing or aberrant remodeling remain largely unknown. Low density lipoprotein receptor-related protein 1 (LRP1) is an endocytic/signaling cell surface receptor which controls cellular and molecular mechanisms driving the physiological and pathological inflammatory reactions and tissue remodeling in several organs...
December 17, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29251594/lrp1-regulates-peroxisome-biogenesis-and-cholesterol-homeostasis-in-oligodendrocytes-and-is-required-for-proper-cns-myelin-development-and-repair
#8
Jing-Ping Lin, Yevgeniya A Mironova, Peter Shrager, Roman J Giger
Low-density lipoprotein receptor-related protein-1 (LRP1) is a large endocytic and signaling molecule broadly expressed by neurons and glia. In adult mice, global inducible (Lrp1flox/flox;CAG-CreER) or oligodendrocyte (OL)-lineage specific ablation (Lrp1flox/flox;Pdgfra-CreER) of Lrp1 attenuates repair of damaged white matter. In oligodendrocyte progenitor cells (OPCs), Lrp1 is required for cholesterol homeostasis and differentiation into mature OLs. Lrp1 deficient OPC/OLs show a strong increase in the sterol-regulatory element-binding protein-2, yet are unable to maintain normal cholesterol levels, suggesting more global metabolic deficits...
December 18, 2017: ELife
https://www.readbyqxmd.com/read/29247679/anti-leptin-receptor-antibodies-strengthen-leptin-biofunction-in-growing-chickens
#9
M M Lei, C K Wei, Z Chen, S Yosefi, H X Zhu, Z D Shi
Antibodies against the extracellular domains of the chicken leptin receptor were used to study the biological function of leptin in growing chickens. Both polyclonal and monoclonal antibodies were administered intramuscularly to 30-d-old Chinese indigenous Gushi pullets. Both antibody preparations increased feed intake for 6 h after injection and reduced plasma concentrations of glucose, triglycerides, and both high- and low-density lipoproteins. The antibody treatments also upregulated agouti-related peptide and neuropeptide Y in the hypothalamus and downregulated proopiomelanocortin, melanocortin 4 receptor, and leptin receptor...
December 13, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29201005/high-concentrations-of-rosiglitazone-reduce-mrna-and-protein-levels-of-lrp1-in-hepg2-cells
#10
Alejandro N Rondón-Ortiz, Christian L Lino Cardenas, Jimena Martínez-Málaga, Ana L Gonzales-Urday, Kuljeet S Gugnani, Mark Böhlke, Timothy J Maher, Alejandro J Pino-Figueroa
Low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic receptor involved in the uptake of a variety of molecules, such as apoE, α2-macroglobulin, and the amyloid β peptide (Aβ), for either transcellular transport, protein trafficking or lysosomal degradation. The LRP1 gene can be transcribed upon activation of peroxisome proliferator receptor activated-γ (PPARγ) by the potent PPARγ agonist, rosiglitazone (RGZ). In previous studies, RGZ was shown to upregulate LRP1 levels in concentrations between 0...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29195136/oxidized-ldl-triggers-changes-in-oxidative-stress-and-inflammatory-biomarkers-in-human-macrophages
#11
Oscar J Lara-Guzmán, Ángel Gil-Izquierdo, Sonia Medina, Edison Osorio, Rafael Álvarez-Quintero, Natalia Zuluaga, Camille Oger, Jean-Marie Galano, Thierry Durand, Katalina Muñoz-Durango
Oxidized low-density lipoprotein (oxLDL) is a well-recognized proatherogenic particle that functions in atherosclerosis. In this study, we established conditions to generate human oxLDL, characterized according to the grade of lipid and protein oxidation, particle size and oxylipin content. The induction effect of the cellular proatherogenic response was assessed in foam cells by using an oxLDL-macrophage interaction model. Uptake of oxLDL, reactive oxygen species production and expression of oxLDL receptors (CD36, SR-A and LOX-1) were significantly increased in THP-1 macrophages...
November 22, 2017: Redox Biology
https://www.readbyqxmd.com/read/29191087/neuroprotective-effect-of-formononetin-in-ameliorating-learning-and-memory-impairment-in-mouse-model-of-alzheimer-s-disease
#12
Hong-Xin Fei, Ying-Bo Zhang, Ting Liu, Xiao-Jie Zhang, Shu-Liang Wu
Alzheimer's disease (AD) is the most common cause of dementia among elderly population. Deranged β-amyloid (Aβ) trafficking across the blood-brain barrier is known to be a critical element in the pathogenesis of AD. In the vascular endothelial cells of hippocampus, Aβ transport is mainly mediated by low-density lipoprotein-associated protein 1 (LRP1) and the receptor for advanced glycation end (RAGE) products; therefore, LRP1 and RAGE endothelial cells are potential therapeutic targets for AD. In this study, we explored the effects of Formononetin (FMN) on learning and memory improvement in APP/PS1 mice and the related mechanisms...
December 1, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29183623/role-of-angiopoietin-like-3-angptl3-in-regulating-plasma-level-of-low-density-lipoprotein-cholesterol
#13
Yu-Xin Xu, Valeska Redon, Haojie Yu, William Querbes, James Pirruccello, Abigail Liebow, Amy Deik, Kevin Trindade, Xiao Wang, Kiran Musunuru, Clary B Clish, Chad Cowan, Kevin Fizgerald, Daniel Rader, Sekar Kathiresan
BACKGROUND AND AIMS: Angiopoietin-like 3 (ANGPTL3) has emerged as a key regulator of lipoprotein metabolism in humans. Homozygous loss of ANGPTL3 function causes familial combined hypolipidemia characterized by low plasma levels of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). While known effects of ANGPTL3 in inhibiting lipoprotein lipase and endothelial lipase contribute to the low TG and HDL-C, respectively, the basis of low LDL-C remains unclear...
September 21, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29182025/vegf-mediated-tight-junctions-pathological-fenestration-enhances-doxorubicin-loaded-glycolipid-like-nanoparticles-traversing-bbb-for-glioblastoma-targeting-therapy
#14
Lijuan Wen, Yanan Tan, Suhuan Dai, Yun Zhu, Tingting Meng, Xiqin Yang, Yupeng Liu, Xuan Liu, Hong Yuan, Fuqiang Hu
The existence of blood-brain barrier (BBB) greatly hindered the penetration and accumulation of chemotherapeutics into glioblastoma (GBM), accompany with poor therapeutic effects. The growth of GBM supervene the impairment of tight junctions (TJs); however, the pathogenesis of BBB breakdown in GBM is essentially poorly understood. This study found that vascular endothelial growth factor (VEGF) secreted by GBM cells plays an important role in increasing the permeability of BBB by disrupting endothelial tight junction proteins claudin-5 and thus gave doxorubicin (DOX)-loaded glycolipid-like nanoparticles (Ap-CSSA/DOX), an effective entrance to brain tumor region for GBM-targeting therapy...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29155576/chronic-arsenic-exposure-increases-a%C3%AE-1-42-production-and-rage-expression-in-rat-brain
#15
Sandra Aurora Niño, Guadalupe Martel-Gallegos, Adriana Castro-Zavala, Benita Ortega-Berlanga, Juan Manuel Delgado, Hector Hernandez-Mendoza, E Romero-Guzman, Judith Rios-Lugo, Sergio Rosales-Mendoza, María Esther Jiménez-Capdeville, Sergio Zarazua
Chronic arsenic exposure during development is associated with alterations of chemical transmission and demyelination, which result in cognitive deficits and peripheral neuropathies. At cellular level, arsenic toxicity involves increased generation of reactive species that induce severe cellular alterations such as DNA fragmentation, apoptosis and lipid peroxidation. It has been proposed that arsenic-associated neurodegeneration could evolve to Alzheimer disease in later life.1,2 In this study, the effects of chronic exposure to inorganic arsenic (3 ppm by drinking water) in Wistar rats on the production and elimination of Amyloid-β (Aβ) were evaluated...
November 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29153781/genetic-epidemiology-of-autosomal-recessive-hypercholesterolemia-in-sicily-identification-by-next-generation-sequencing-of-a-new-kindred
#16
Rossella Spina, Davide Noto, Carlo M Barbagallo, Roberto Monastero, Valeria Ingrassia, Vincenza Valenti, Roberta Baschi, Antonina Pipitone, Antonina Giammanco, Maria P La Spada, Gabriella Misiano, Chiara Scrimali, Angelo B Cefalù, Maurizio R Averna
BACKGROUND: Autosomal recessive hypercholesterolemia (ARH) is a rare inherited lipid disorder. In Sardinia, differently from other world regions, the mutated allele frequency is high. It is caused by mutations in the low-density lipoprotein receptor adaptor protein 1 gene. Fourteen different mutations have been reported so far; in Sardinia, 2 alleles (ARH1 and ARH2) explain most of the cases. Four ARH patients, all carriers of the ARH1 mutation, have been identified in mainland Italy and 2 in Sicily...
October 27, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29144234/lrp1-integrates-murine-macrophage-cholesterol-homeostasis-and-inflammatory-responses-in-atherosclerosis
#17
Xunde Xian, Yinyuan Ding, Marco Dieckmann, Li Zhou, Florian Plattner, Mingxia Liu, John S Parks, Robert E Hammer, Philippe Boucher, Shirling Tsai, Joachim Herz
Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional cell surface receptor with diverse physiological roles, ranging from cellular uptake of lipoproteins and other cargo by endocytosis to sensor of the extracellular environment and integrator of a wide range of signaling mechanisms. As a chylomicron remnant receptor, LRP1 controls systemic lipid metabolism in concert with the LDL receptor in the liver, whereas in smooth muscle cells (SMC) LRP1 functions as a co-receptor for TGFβ and PDGFRβ in reverse cholesterol transport and the maintenance of vascular wall integrity...
November 16, 2017: ELife
https://www.readbyqxmd.com/read/29138479/yes-associated-protein-yap-promotes-tumorigenesis-in-melanoma-cells-through-stimulation-of-low-density-lipoprotein-receptor-related-protein-1-lrp1
#18
Huizi Xiong, Qian Yu, Yu Gong, Wenjuan Chen, Yunlei Tong, Yao Wang, Hui Xu, Yuling Shi
YAP is a critical protein in cancer development and can induce transformative phenotypes in mammary epithelial cells. Previous studies have provided evidence that YAP can contribute to the metastatic behavior of melanoma, since specific knockdown of YAP leads to reduced metastatic and invasive capacity in vitro. However, the mechanism by which YAP regulates the function of melanoma is unknown. Here, we identified that YAP has a positive impact on the expression of LRP1, which also plays critical roles in cancer...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29131552/activation-of-the-wnt-pathway-by-small-peptides-rational-design-synthesis-and-biological-evaluation
#19
Simone Brogi, Samuele Maramai, Margherita Brindisi, Giulia Chemi, Valentina Porcari, Claudio Corallo, Luigi Gennari, Ettore Novellino, Anna Ramunno, Stefania Butini, Giuseppe Campiani, Sandra Gemma
A computational analysis of the X-ray structure of the low-density lipoprotein receptor-related protein 6 (LRP6) with Dickkopf-1 (DKK1) C-terminal fragment has allowed us to rationally design a small set of decapeptides (1a-e). These compounds behave as agonists of the canonical Wnt pathway in the micromolar range when tested on a dual luciferase Wnt functional assay in glioblastoma cells. Lack of cellular toxicity was assessed for compounds 1c and 1d in human primary osteoblasts isolated from sponge bone tissue (femoral heads or knee of old patients)...
November 13, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29124655/enhanced-bioactivity-of-the-anti-lox-1-scfv-engineered-by-multimerization-strategy
#20
Wei Hu, Qiuhong Xie, Ling Liu, Hongyu Xiang
Single-chain variable fragment (scFv) antibodies as therapeutic agents have the potential to reduce the production cost and immunogenicity relative to monoclonal antibodies, but their monovalency and lack of a fragment crystallizable region can lead to reduced function. Multimerization is one strategy for recovering the function; however, their application is limited by the production of multimeric proteins. In our previous study, an anti-lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) scFv showed potential use in diagnosis and therapy of atherosclerotic diseases, but is limited by its inherent low antigen-binding activity...
November 9, 2017: Applied Biochemistry and Biotechnology
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