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https://www.readbyqxmd.com/read/29348672/soluble-lrp1-is-an-independent-biomarker-of-epicardial-fat-volume-in-patients-with-type-1-diabetes-mellitus
#1
David de Gonzalo-Calvo, Cristina Colom, David Vilades, Andrea Rivas-Urbina, Abdel-Hakim Moustafa, Montserrat Pérez-Cuellar, Jose Luis Sánchez-Quesada, Antonio Pérez, Vicenta LLorente-Cortes
Epicardial adipose tissue (EAT) is a metabolically active tissue intimately associated with metabolic syndrome and cardiovascular disease. Quantification of EAT volume is an interesting clinical tool for the evaluation of cardiometabolic disease. Nevertheless, current methodology presents serious disadvantages. The soluble form of the receptor LRP1 (sLRP1) is a non-invasive biomarker of EAT in general population. Here, we analysed the potential of circulating sLRP1 as biomarker of EAT volume in patients with type 1 diabetes mellitus (T1DM)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29278306/haematoma-scavenging-in-intracerebral-haemorrhage-from-mechanisms-to-the-clinic
#2
REVIEW
Gaiqing Wang, Li Wang, Xin-Gang Sun, Jiping Tang
The products of erythrocyte lyses, haemoglobin (Hb) and haem, are recognized as neurotoxins and the main contributors to delayed cerebral oedema and tissue damage after intracerebral haemorrhage (ICH). Finding a means to efficiently promote absorption of the haemolytic products (Hb and haem) around the bleeding area in the brain through stimulating the function of the body's own garbage cleaning system is a novel clinical challenge and critical for functional recovery after ICH. In this review, available information of the brain injury mechanisms underlying ICH and endogenous haematoma scavenging system is provided...
December 26, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29262309/lrp1-a-chameleon-receptor-of-lung-inflammation-and-repair
#3
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
#4
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/29201005/high-concentrations-of-rosiglitazone-reduce-mrna-and-protein-levels-of-lrp1-in-hepg2-cells
#5
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/29191087/neuroprotective-effect-of-formononetin-in-ameliorating-learning-and-memory-impairment-in-mouse-model-of-alzheimer-s-disease
#6
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/29182025/vegf-mediated-tight-junctions-pathological-fenestration-enhances-doxorubicin-loaded-glycolipid-like-nanoparticles-traversing-bbb-for-glioblastoma-targeting-therapy
#7
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/29170124/long-non-coding-rna-lucat1-modulates-methotrexate-resistance-in-osteosarcoma-via-mir-200c-abcb1-axis
#8
Zhe Han, Liying Shi
Long non-coding RNAs (lncRNAs) have been verified to participate in the tumorigenesis of multiple cancers. Nevertheless, the deepgoing role molecular mechanisms of lncRNAs on osteosarcoma chemoresistance remain unclear. In present study, we investigate the function of lncRNA LUCAT1 on osteosarcoma methotrexate (MTX) resistant phenotype and discover the potential regulatory mechanism. Results showed that LUCAT1 was up-regulated in MTX-resistant cells (MG63/MTX, HOS/MTX) compared to that in parental cells. LncRNA LUCAT1 and ABCB1 protein expression levels were both up-regulated when induced by different concentration of methotrexate...
November 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29155576/chronic-arsenic-exposure-increases-a%C3%AE-1-42-production-and-rage-expression-in-rat-brain
#9
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/29146996/the-role-of-cxcr3-lrp1-cross-talk-in-the-invasion-of-primary-brain-tumors
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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