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https://www.readbyqxmd.com/read/29146996/the-role-of-cxcr3-lrp1-cross-talk-in-the-invasion-of-primary-brain-tumors
#1
Kevin Boyé, Nadège Pujol, Isabel D Alves, Ya-Ping Chen, Thomas Daubon, Yi-Zong Lee, Stephane Dedieu, Marion Constantin, Lorenzo Bello, Marco Rossi, Rolf Bjerkvig, Shih-Che Sue, Andreas Bikfalvi, Clotilde Billottet
CXCR3 plays important roles in angiogenesis, inflammation, and cancer. However, the precise mechanism of regulation and activity in tumors is not well known. We focused on CXCR3-A conformation and on the mechanisms controlling its activity and trafficking and investigated the role of CXCR3/LRP1 cross talk in tumor cell invasion. Here we report that agonist stimulation induces an anisotropic response with conformational changes of CXCR3-A along its longitudinal axis. CXCR3-A is internalized via clathrin-coated vesicles and recycled by retrograde trafficking...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29144234/lrp1-integrates-murine-macrophage-cholesterol-homeostasis-and-inflammatory-responses-in-atherosclerosis
#2
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
#3
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/29116364/low-density-lipoprotein-receptor-related-protein-1-couples-%C3%AE-1-integrin-activation-to-degradation
#4
Lukasz Wujak, Ralph T Böttcher, Oleg Pak, Helena Frey, Elie El Agha, Ying Chen, Sigrid Schmitt, Saverio Bellusci, Liliana Schaefer, Norbert Weissmann, Reinhard Fässler, Malgorzata Wygrecka
Low density lipoprotein receptor-related protein (LRP) 1 modulates cell adhesion and motility under normal and pathological conditions. Previous studies documented that LRP1 binds several integrin receptors and mediates their trafficking to the cell surface and endocytosis. However, the mechanism by which LRP1 may regulate integrin activation remains unknown. Here we report that LRP1 promotes the activation and subsequent degradation of β1 integrin and thus supports cell adhesion, spreading, migration and integrin signaling on fibronectin...
November 7, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29108253/identification-of-lrp-1-as-an-endocytosis-and-recycling-receptor-for-%C3%AE-1-integrin-in-thyroid-cancer-cells
#5
Louis Theret, Albin Jeanne, Benoit Langlois, Cathy Hachet, Marion David, Michel Khrestchatisky, Jérôme Devy, Emonard Hervé, Sébastien Almagro, Stéphane Dedieu
LRP-1 is a large endocytic receptor mediating the clearance of various molecules from the extracellular matrix. LRP-1 was reported to control focal adhesion turnover to optimize the adhesion-deadhesion balance to support invasion. To better understand how LRP-1 coordinates cell-extracellular matrix interface, we explored its ability to regulate cell surface integrins in thyroid carcinomas. Using an antibody approach, we demonstrated that β1-integrin levels were increased at the plasma membrane under LRP1 silencing or upon RAP treatment, used as LRP-1 antagonist...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29106980/pericyte-implantation-in-the-brain-enhances-cerebral-blood-flow-and-reduces-amyloid-%C3%AE-pathology-in-amyloid-model-mice
#6
Masaya Tachibana, Yu Yamazaki, Chia-Chen Liu, Guojun Bu, Takahisa Kanekiyo
Pericytes are a major component of cerebrovasculature playing a key role in maintaining cerebrovascular homeostasis. These cells have also been suggested to regulate brain metabolism of amyloid-β (Aβ), disturbances of which are believed to contribute to the pathogenesis of Alzheimer's disease (AD). To examine the effects of pericytes on brain Aβ metabolism, C3H/10T1/2 mouse mesenchymal stem cells were differentiated into pericytes and stereotaxically injected into the brains of amyloid AD model APP/PS1 mice at the age of 18 to 20months...
October 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29090274/a-novel-lrp1-binding-peptide-l57-that-crosses-the-blood-brain-barrier
#7
Kotaro Sakamoto, Tokuyuki Shinohara, Yusuke Adachi, Taiji Asami, Tetsuya Ohtaki
The blood-brain barrier (BBB) is a major obstacle to drug delivery into the central nervous system (CNS), in particular for macromolecules such as peptides and proteins. However, certain macromolecules can reach the CNS via a receptor-mediated transcytosis (RMT) pathway, and low-density lipoprotein receptor-related protein 1 (LRP1) is one of the promising receptors for RMT. An LRP1 ligand peptide, Angiopep-2, was reported to pass through the BBB and deliver covalently conjugated drugs into the CNS. While conjugation of LRP1 ligands with drugs would be an effective approach for drug delivery to the CNS, no other reliable LRP1 ligands have been reported to date...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29084210/zeb1-repressed-micrornas-inhibit-autocrine-signaling-that-promotes-vascular-mimicry-of-breast-cancer-cells
#8
E M Langer, N D Kendsersky, C J Daniel, G M Kuziel, C Pelz, K M Murphy, M R Capecchi, R C Sears
During normal tumor growth and in response to some therapies, tumor cells experience acute or chronic deprivation of nutrients and oxygen and induce tumor vascularization. While this occurs predominately through sprouting angiogenesis, tumor cells have also been shown to directly contribute to vessel formation through vascular mimicry (VM) and/or endothelial transdifferentiation. The extrinsic and intrinsic mechanisms underlying tumor cell adoption of endothelial phenotypes, however, are not well understood...
October 30, 2017: Oncogene
https://www.readbyqxmd.com/read/29079999/trafficking-in-alzheimer-s-disease-modulation-of-app-transport-and-processing-by-the-transmembrane-proteins-lrp1-sorla-sorcs1c-sortilin-and-calsyntenin
#9
REVIEW
Simone Eggert, Carolin Thomas, Stefan Kins, Guido Hermey
The amyloid precursor protein (APP), one key player in Alzheimer's disease (AD), is extensively processed by different proteases. This leads to the generation of diverging fragments including the amyloid β (Aβ) peptide, which accumulates in brains of AD patients. Subcellular trafficking of APP is an important aspect for its proteolytic conversion, since the various secretases which cleave APP are located in different cellular compartments. As a consequence, altered subcellular targeting of APP is thought to directly affect the degree to which Aβ is generated...
October 27, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29028290/plasminogen-activator-inhibitor-1-regulates-the-vascular-expression-of-vitronectin
#10
M Luo, Y Ji, Y Luo, R Li, W P Fay, J Wu
Essentials Vitronectin (VN) is produced by smooth muscle cells (SMCs) and promotes neointima formation. We studied the regulation of vascular VN expression by plasminogen activator inhibitor-1 (PAI-1). PAI-1 stimulates VN gene expression in SMCs by binding LDL receptor-related protein 1. Stimulation of VN gene expression may be a mechanism by which PAI-1 controls vascular remodeling. SUMMARY: Background Increased expression of vitronectin (VN) by smooth muscle cells (SMCs) promotes neointima formation after vascular injury, and may contribute to chronic vascular diseases, such as atherosclerosis...
October 13, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29021777/circulating-cholesterol-levels-may-link-to-the-factors-influencing-parkinson-s-risk
#11
Lijun Zhang, Xue Wang, Ming Wang, Nick W Sterling, Guangwei Du, Mechelle M Lewis, Tao Yao, Richard B Mailman, Runze Li, Xuemei Huang
OBJECTIVES: A growing literature suggests that circulating cholesterol levels have been associated with Parkinson's disease (PD). In this study, we investigated a possible causal basis for the cholesterol-PD link. METHODS: Fasting plasma cholesterol levels were obtained from 91 PD and 70 age- and gender-matched controls from an NINDS PD Biomarkers Program cohort at the Pennsylvania State University College of Medicine. Based on the literature, genetic polymorphisms in selected cholesterol management genes (APOE, LDLR, LRP1, and LRPAP1) were chosen as confounding variables because they may influence both cholesterol levels and PD risk...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28972143/shedding-of-membrane-associated-ldl-receptor-related-protein-1-from-microglia-amplifies-and-sustains-neuroinflammation
#12
Coralie Brifault, Andrew S Gilder, Emilia Laudati, Michael Banki, Steven L Gonias
In the CNS, microglia are activated in response to injury or infection and in neurodegenerative diseases. The endocytic and cell signaling receptor, LDL receptor-related protein-1 (LRP1), is reported to suppress innate immunity in macrophages and oppose microglial activation. The goal of this study was to identify novel mechanisms by which LRP1 may regulate microglial activation. Using primary cultures of microglia isolated from mouse brains, we demonstrated that LRP1 gene silencing increases expression of proinflammatory mediators; however, the observed response was modest...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28952330/genome-wide-association-study-identifies-novel-susceptibility-loci-for-migraine-in-han-chinese-resided-in-taiwan
#13
Shih-Pin Chen, Jong-Ling Fuh, Ming-Yi Chung, Ying-Chao Lin, Yi-Chu Liao, Yen-Feng Wang, Chia-Lin Hsu, Ueng-Cheng Yang, Ming-Wei Lin, Jen-Jie Chiou, Po-Jen Wang, Ping-Kun Chen, Pi-Chuan Fan, Jer-Yuan Wu, Yuan-Tsong Chen, Lung-Sen Kao, Cathy Shen-Jang Fann, Shuu-Jiun Wang
Background Susceptibility genes for migraine, despite it being a highly prevalent and disabling neurological disorder, have not been analyzed in Asians by genome-wide association study (GWAS). Methods We conducted a two-stage case-control GWAS to identify susceptibility genes for migraine without aura in Han Chinese residing in Taiwan. In the discovery stage, we genotyped 1005 clinic-based Taiwanese migraine patients and 1053 population-based sex-matched controls using Axiom Genome-Wide CHB Array. In the replication stage, we genotyped 27 single-nucleotide polymorphisms with p < 10(-4) in 1120 clinic-based migraine patients and 604 sex-matched normal controls by using Sequenom...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28948494/endothelial-lrp1-a-potential-target-for-the-treatment-of-alzheimer-s-disease
#14
REVIEW
Steffen E Storck, Claus U Pietrzik
The accumulation of the neurotoxin beta-amyloid (Aβ) is a major hallmark in Alzheimer's disease (AD). Aβ homeostasis in the brain is governed by its production and various clearance mechanisms. Both pathways are influenced by the ubiquitously expressed low-density lipoprotein receptor-related protein 1 (LRP1). In cerebral blood vessels, LRP1 is an important mediator for the rapid removal of Aβ from brain via transport across the blood-brain barrier (BBB). Here, we summarize recent findings on LRP1 function and discuss the targeting of LRP1 as a modulator for AD pathology and drug delivery into the brain...
September 25, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28941799/regulatory-effects-of-simvastatin-and-apoj-on-app-processing-and-amyloid-%C3%AE-clearance-in-blood-brain-barrier-endothelial-cells
#15
Martina Zandl-Lang, Elham Fanaee-Danesh, Yidan Sun, Nicole M Albrecher, Chaitanya Chakravarthi Gali, Igor Čančar, Alexandra Kober, Carmen Tam-Amersdorfer, Anika Stracke, Steffen M Storck, Ahmed Saeed, Jasminka Stefulj, Claus U Pietrzik, Mark R Wilson, Ingemar Björkhem, Ute Panzenboeck
Amyloid-β peptides (Aβ) accumulate in cerebral capillaries indicating a central role of the blood-brain barrier (BBB) in the pathogenesis of Alzheimer's disease (AD). Although a relationship between apolipoprotein-, cholesterol- and Aβ metabolism is evident, the interconnecting mechanisms operating in brain capillary endothelial cells (BCEC) are poorly understood. ApoJ (clusterin) is present in HDL that regulates cholesterol metabolism which is disturbed in AD. ApoJ levels are increased in AD brains and in plasma of cerebral amyloid angiopathy (CAA) patients...
September 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28931568/a-cross-talk-between-neuronal-urokinase-type-plasminogen-activator-upa-and-astrocytic-upa-receptor-upar-promotes-astrocytic-activation-and-synaptic-recovery-in-the-ischemic-brain
#16
Ariel Diaz, Paola Merino, Luis Guillermo Manrique, Juan Pablo Ospina, Lihong Cheng, Fang Wu, Valerie Jeanneret, Manuel Yepes
Urokinase-type plasminogen activator (uPA) is a serine proteinase that, upon binding to its receptor (uPAR), catalyzes the conversion of plasminogen into plasmin on the cell surface. Our previous studies indicate that uPA and uPAR expression increase in the ischemic brain during the recovery phase from an acute ischemic injury and that uPA binding to uPAR promotes neurological recovery after an acute ischemic stroke. Here, we used male mice genetically deficient on either uPA (uPA(-/-)) or uPAR (uPAR(-/-)) or with a four-amino acid substitution into the growth factor domain of uPA that abrogates its binding to uPAR (Plat(GFDhu/GFDhu)) to investigate the mechanism whereby uPA promotes neurorepair in the ischemic brain...
October 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28924541/the-lrp1-gene-polymorphism-is-associated-with-increased-risk-of-metabolic-syndrome-prevalence-in-the-serbian-population
#17
N Vučinić, E Stokić, I Djan, D Obreht, N Veličković, K Stankov, M Djan
The determination of genetic background in metabolic syndrome (MetS) represents one of the necessary steps to prevent the disorder, thus reducing the cost of medical treatments and helping to design targeted therapy. The study explores the association between individual alleles of the LRP1 gene and the diagnosis of MetS to find correlation between the low-density lipoprotein receptor-related (LRP1) gene polymorphism and each individual anthropometric and biochemical parameter. The study included 93 males and females, aged from 19 to 65, divided into two groups...
June 30, 2017: Balkan Journal of Medical Genetics: BJMG
https://www.readbyqxmd.com/read/28901468/apolipoprotein-a5-regulates-intracellular-triglyceride-metabolism-in-adipocytes
#18
Xiao-Yan Zheng, Bi-Lian Yu, Yu-Fei Xie, Shui-Ping Zhao, Chen-Lu Wu
It has previously been demonstrated that apolipoprotein A5 (apoA5) can be internalized by human adipocytes and significantly decreases intracellular triglyceride content. In the present study, endocytosis of apoA5 by adipocytes under different conditions, and the underlying mechanism by which apoA5 regulates cellular triglyceride storage, was investigated. The results revealed that the apoA5 protein was detected in human subcutaneous abdominal adipose tissues. In addition, the uptake of apoA5 was attenuated in human obese adipose tissues and in cultured adipocytes with hypertrophy or insulin resistance...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28892789/thymoquinone-rich-fraction-nanoemulsion-tqrfne-decreases-a%C3%AE-40-and-a%C3%AE-42-levels-by-modulating-app-processing-up-regulating-ide-and-lrp1-and-down-regulating-bace1-and-rage-in-response-to-high-fat-cholesterol-diet-induced-rats
#19
Norsharina Ismail, Maznah Ismail, Nur Hanisah Azmi, Muhammad Firdaus Abu Bakar, Zhang Yida, Maizaton Atmadini Abdullah, Hamidon Basri
Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-β (Aβ) accumulation due to abnormal amyloid-β precursor protein (APP) processing and Aβ metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aβ metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28867180/lactoferrin-promotes-autophagy-via-amp-activated-protein-kinase-activation-through-low-density-lipoprotein-receptor-related-protein-1
#20
Shu Aizawa, Minami Hoki, Yutaka Yamamuro
Lactoferrin (LF) is a multifunctional, iron-binding glycoprotein in mammalian secretions, such as breast milk, and has several beneficial effects for human health. However, how these effects are exerted at the cellular level is still largely unknown. In this study, we investigated the effects of LF on autophagy activity in NIH/3T3 mouse fibroblasts. LF from bovine milk was found to increase LC3-I to LC3-II conversion and LC3-positive cytosolic punctate structures because of increased autophagy flux. Knockdown of the putative LF receptor low-density receptor-related protein 1 (LRP1) completely abolished LC3 conversion in cells by LF treatment...
November 4, 2017: Biochemical and Biophysical Research Communications
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