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https://www.readbyqxmd.com/read/28699828/glioma-targeted-delivery-strategy-of-doxorubicin-loaded-liposomes-by-dual-ligand-modification
#1
Wei Han, Guangfu Yin, Ximing Pu, Xianchun Chen, Xiaoming Liao, Zhongbing Huang
The blood-brain barrier (BBB) is the protective parclose of brain safety, but it is also the main obstacle of the drug delivery to cerebral parenchyma, which hamper therapy for brain diseases. In this work, a glioma targeted drug delivery system was developed through loading doxorubicin into Angiopep-2 and TAT peptide dual-modified liposomes (DOX-TAT-Ang-LIP). Low-density lipoprotein receptor-related protein-1 (LRP1) was one receptor overexpressed on both BBB and glioma cytomembranes. Angiopep-2, a specific ligand of LRP1, exhibited high LRP1 binding efficiency...
July 12, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28698188/a-dab2ip-genotype-sex-interaction-is-associated-with-abdominal-aortic-aneurysm-expansion
#2
Zi Ye, Erin Austin, Daniel J Schaid, Kent R Bailey, Patricia A Pellikka, Iftikhar J Kullo
A faster expansion rate of abdominal aortic aneurysm (AAA) increases the risk of rupture. Women are at higher risk of rupture than men, but the mechanisms underlying this increased risk are unknown. We investigated whether genetic variants that influence susceptibility for AAA (CDKN2A-2B, SORT1, DAB2IP, LRP1 and LDLR) are associated with AAA expansion and whether these associations differ by sex in 650 patients with AAA (mean age 70±8 years, 17% women) enrolled in the Mayo Clinic Vascular Disease Biorepository...
July 11, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28684538/tissue-type-plasminogen-activator-regulates-macrophage-activation-and-innate-immunity
#3
Elisabetta Mantuano, Pardis Azmoon, Coralie Brifault, Michael A Banki, Andrew S Gilder, Wendy M Campana, Steven L Gonias
Tissue-type plasminogen activator (tPA) is the major intravascular activator of fibrinolysis and a ligand for receptors involved in cell-signaling. In cultured macrophages, tPA inhibits the response to lipopolysaccharide (LPS) by a pathway that apparently requires LDL Receptor-related Protein-1 (LRP1). Herein, we show that the mechanism by which tPA neutralizes LPS involves rapid reversal of IκBα phosphorylation. tPA independently induced transient IκBα phosphorylation and ERK1/2 activation in macrophages; however, these events that did not trigger inflammatory mediator expression...
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28669880/role-of-vitamin-d-in-amyloid-clearance-via-lrp-1-upregulation-in-alzheimer-s-disease-a-potential-therapeutic-target
#4
REVIEW
Parmi Patel, Jigna Shah
Amyloid beta (Aβ) deposition is considered to be one of the primary reason to trigger Alzheimer's disease (AD). Literature clearly suggests decline in Aβ clearance to be accountable for progression of late onset AD as compared to augmented Aβ production. There may be several pathways for Aβ clearance out of which one of the major pathway is the vascular-mediated removal of Aβ from the brain across the blood-brain barrier (BBB) via efflux pumps or receptors. Among Aβ scavenger receptors, low density lipoprotein receptor related protein (LRP-1) has been most extensively studied...
June 30, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28668966/long-non-coding-rna-malat1-decreases-the-sensitivity-of-resistant-glioblastoma-cell-lines-to-temozolomide
#5
Hongwei Li, Xiaoli Yuan, Dongming Yan, Dongpeng Li, Fangxia Guan, Yang Dong, Hao Wang, Xianzhi Liu, Bo Yang
BACKGROUND/AIM: Multidrug resistance (MDR) is largely responsible for the failure of chemotherapy. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript (MALAT1) has been reported to be closely related to tumor biology. In the present study, whether MALAT1 contributes to the resistance of glioblastoma cell lines to temozolomide (TMZ) was investigated. METHODS: The glioblastoma cell lines U251 and U87 were exposed to increasing concentrations of TMZ to generate TMZ-resistant colonies (the U251/TMZ and U87/TMZ cell lines)...
July 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28662213/verification-and-characterization-of-an-alternative-low-density-lipoprotein-receptor-related-protein-1-splice-variant
#6
Marlen Kolb, Susanne Kurz, Angelika Schäfer, Klaus Huse, Andreas Dietz, Gunnar Wichmann, Gerd Birkenmeier
BACKGROUND: Low density lipoprotein (LDL) receptor-related protein 1 (LRP1) is a ubiquitously expressed multi-ligand endocytosis receptor implicated in a wide range of signalling, among others in tumour biology. Tumour-associated genomic mutations of the LRP1 gene are described, but nothing is known about cancer-associated expression of LRP1 splice variants Therefore, the focus of this study was on an annotated truncated LRP1 splice variant (BC072015.1; NCBI GenBank), referred to as smLRP1, which was initially identified in prostate and lung carcinoma...
2017: PloS One
https://www.readbyqxmd.com/read/28656081/effect-of-rosiglitazone-on-amyloid-precursor-protein-processing-and-a%C3%AE-clearance-in-streptozotocin-induced-rat-model-of-alzheimer-s-disease
#7
Li Wang, Wei Liu, Ying Fan, Tingting Liu, Chunjiang Yu
OBJECTIVES: Increasing evidence suggests that Alzheimer's disease (AD) is associated with diabetes. Rosiglitazone, a peroxisome proliferator-activated receptor γ (PPAR-γ) agonist and anti-diabetic agent, may improve symptoms of AD. However, the underlying therapeutic potential of it has not been fully elucidated. MATERIALS AND METHODS: Rats were divided into four groups: control group, sham operated group, Streptozotocin (STZ) group, rosiglitazone (RGZ) group...
May 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28623956/differential-protein-expression-in-chicken-macrophages-and-heterophils-in-vivo-following-infection-with-salmonella-enteritidis
#8
Zuzana Sekelova, Hana Stepanova, Ondrej Polansky, Karolina Varmuzova, Marcela Faldynova, Radek Fedr, Ivan Rychlik, Lenka Vlasatikova
In this study we compared the proteomes of macrophages and heterophils isolated from the spleen 4 days after intravenous infection of chickens with Salmonella Enteritidis. Heterophils were characterized by expression of MMP9, MRP126, LECT2, CATHL1, CATHL2, CATHL3, LYG2, LYZ and RSFR. Macrophages specifically expressed receptor proteins, e.g. MRC1L, LRP1, LGALS1, LRPAP1 and a DMBT1L. Following infection, heterophils decreased ALB and FN1, and released MMP9 to enable their translocation to the site of infection...
June 17, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28612181/low-density-lipoprotein-receptor-related-protein-1-lrp1-c4408r-mutant-promotes-amyloid-precursor-protein-app-%C3%AE-cleavage-in-vitro
#9
Huayan Hou, Ahsan Habib, Dan Zi, Kathy Tian, Jun Tian, Brian Giunta, Darrell Sawmiller, Jun Tan
Previous studies have demonstrated that the low-density lipoprotein receptor-related protein-1 (LRP1) plays conflicting roles in Alzheimer's disease (AD) pathogenesis, clearing β-amyloid (Aβ) from the brain while also enhancing APP endocytosis and resultant amyloidogenic processing. We have recently discovered that co-expression of mutant LRP1 C-terminal domain (LRP1-CT C4408R) with Swedish mutant amyloid precursor protein (APPswe) in Chinese hamster ovary (CHO) cells decreases Aβ production, while also increasing sAPPα and APP α-C-terminal fragment (α-CTF), compared with CHO cells expressing APPswe alone...
June 13, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28596374/lrp1-dependent-bmper-signaling-regulates-lipopolysaccharide-induced-vascular-inflammation
#10
Pamela Lockyer, Hua Mao, Qiying Fan, Luge Li, Li-Yuan Yu-Lee, N Tony Eissa, Cam Patterson, Liang Xie, Xinchun Pi
OBJECTIVE: Bacterial endotoxin (lipopolysaccharide)-mediated sepsis involves dysregulated systemic inflammation, which injures the lung and other organs, often fatally. Vascular endothelial cells act as both targets and mediators of lipopolysaccharide-induced inflammatory responses. Dysfunction of endothelium results in increases of proinflammatory cytokine production and permeability leakage. BMPER (bone morphogenetic protein-binding endothelial regulator), an extracellular modulator of bone morphogenetic protein signaling, has been identified as a vital component in chronic endothelial inflammatory responses and atherosclerosis...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28589128/low-density-lipoprotein-receptor-related-protein-1-signaling-in-angiogenesis
#11
REVIEW
Hua Mao, Liang Xie, Xinchun Pi
Low-density lipoprotein receptor-related protein-1 (LRP1) plays multifunctional roles in lipid homeostasis, signaling transduction, and endocytosis. It has been recognized as an endocytic receptor for many ligands and is involved in the signaling pathways of many growth factors or cytokines. Dysregulation of LRP1-dependent signaling events contributes to the development of pathophysiologic processes such as Alzheimer's disease, atherosclerosis, inflammation, and coagulation. Interestingly, recent studies have linked LRP1 with endothelial function and angiogenesis, which has been underappreciated for a long time...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28588032/inactivation-of-%C3%AE-secretases-leads-to-accumulation-of-substrates-and-non-alzheimer-neurodegeneration
#12
Hermien Acx, Lutgarde Serneels, Enrico Radaelli, Serge Muyldermans, Cécile Vincke, Elise Pepermans, Ulrike Müller, Lucía Chávez-Gutiérrez, Bart De Strooper
γ-Secretases are a family of intramembrane cleaving aspartyl proteases and important drug targets in Alzheimer's disease. Here, we generated mice deficient for all γ-secretases in the pyramidal neurons of the postnatal forebrain by deleting the three anterior pharynx defective 1 (Aph1) subunits (Aph1abc cKO Cre(+)). The mice show progressive cortical atrophy, neuronal loss, and gliosis. Interestingly, this is associated with more than 10-fold accumulation of membrane-bound fragments of App, Aplp1, Nrg1, and Dcc, while other known substrates of γ-secretase such as Aplp2, Lrp1, and Sdc3 accumulate to lesser extents...
June 6, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28584820/the-ldl-receptor-related-protein-1-at-the-crossroads-of-lipoprotein-metabolism-and-insulin-signaling
#13
REVIEW
Dianaly T Au, Dudley K Strickland, Selen C Muratoglu
The metabolic syndrome is an escalating worldwide public health concern. Defined by a combination of physiological, metabolic, and biochemical factors, the metabolic syndrome is used as a clinical guideline to identify individuals with a higher risk for type 2 diabetes and cardiovascular disease. Although risk factors for type 2 diabetes and cardiovascular disease have been known for decades, the molecular mechanisms involved in the pathophysiology of these diseases and their interrelationship remain unclear...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28580688/t-cell-regulation-through-a-basic-suppressive-mechanism-targeting-low-density-lipoprotein-receptor-related-protein-1
#14
Jeneen Panezai, Eva Bergdahl, Karl-Gösta Sundqvist
Cell adhesion is generally considered to depend on positive regulation through ligation of integrins and cytokine receptors. However, here we show that T cell adhesion, and notably also TCR-induced activation, are subject to constant suppression through shedding of low density lipoprotein receptor-related protein1 (LRP1). The broad-spectrum metalloprotease inhibitor GM6001 abrogated shedding thus inducing prominent cell surface expression of LRP1 while enhancing TCR-induced activation and adhesion to β1 and β2 integrin ligands, hence arresting the cells...
June 5, 2017: Immunology
https://www.readbyqxmd.com/read/28578378/genome-wide-profiling-of-mirna-and-mrna-expression-in-alzheimer-s-disease
#15
Wan-Sheng Chang, Yong-Hong Wang, Xiao-Tun Zhu, Chuan-Jie Wu
BACKGROUND Our study aimed to identify key differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) which can serve as potential biomarkers for diagnosis and therapy of Alzheimer's disease (AD). MATERIAL AND METHODS We performed miRNA and mRNA integrated analysis (MMIA) to identify DEGs and DEmiRNAs of AD. The AD-specific DEmiRNAs-targets interaction network was contrasted. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed. Q-RT-PCR was used to verify the expression of selected DEGs and DEmiRNAs...
June 4, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28576849/proteome-wide-identification-of-glycosylation-dependent-interactors-of-galectin-1-and-galectin-3-on-mesenchymal-retinal-pigment-epithelial-cells
#16
Jara Obermann, Claudia S Priglinger, Juliane Merl-Pham, Arie Geerlof, Sigfried Priglinger, Magdalena Götz, Stefanie M Hauck
Identification of interactors is a major goal in cell biology. Not only protein-protein but also protein-carbohydrate interactions are of high relevance for signal transduction in biological systems. Here we aim to identify novel interacting binding partners for the β-galactoside-binding proteins Galectin-1 (Gal-1) and Galectin-3 (Gal-3) relevant in the context of the eye disease proliferative vitreoretinopathy (PVR). PVR is one of the most common failures after retinal detachment surgeries and is characterized by the migration, adhesion and epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPE) and the subsequent formation of sub- and epiretinal fibrocellular membranes...
June 2, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28570028/transthyretin-stability-is-critical-in-assisting-beta-amyloid-clearance-relevance-of-transthyretin-stabilization-in-alzheimer-s-disease
#17
Mobina Alemi, Sara C Silva, Isabel Santana, Isabel Cardoso
BACKGROUND: The absence of transthyretin (TTR) in AD mice decreases brain Aβ clearance and reduces the low-density lipoprotein receptor-related protein 1 (LRP1). It is possible that neuroprotection by TTR is dependent on its tetramer structural stability, as studies using TTR mutants showed that unstable L55P TTR has low affinity for Aβ, and TTR tetrameric stabilizers such as iododiflunisal ameliorate AD features in vivo. METHODS: We firstly investigated TTR folding status in human plasma measuring the resistance to urea denaturation...
July 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28558995/cellular-uptake-of-coagulation-factor-viii-elusive-role-of-the-membrane-binding-spikes-in-the-c1-domain
#18
Lydia Castro-Núñez, Johanna M Koornneef, Mariska G Rondaij, Esther Bloem, Carmen van der Zwaan, Koen Mertens, Alexander B Meijer, Henriet Meems
Low density lipoprotein receptor-related protein 1 (LRP1) is involved in the catabolism of many ligands, including factor VIII (FVIII) and alpha-2-macroglobulin (α2M). Transfer of FVIII to LRP1 is currently believed to be preceded by pre-concentration on the cell surface, by interacting with a so far unidentified component. In the present study, we used confocal microscopy and flow cytometry to compare endocytosis of FVIII and α2M using U87MG cells. The results show that α2M is rapidly internalized and does not compete for LRP1 mediated internalization of FVIII...
May 27, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28557183/extracellular-vesicles-do-not-contribute-to-higher-circulating-levels-of-soluble-lrp1-in-idiopathic-dilated-cardiomyopathy
#19
Santiago Roura, Carolina Gálvez-Montón, David de Gonzalo-Calvo, Ana Gámez Valero, Paloma Gastelurrutia, Elena Revuelta-López, Cristina Prat-Vidal, Carolina Soler-Botija, Aida Llucià-Valldeperas, Isaac Perea-Gil, Oriol Iborra-Egea, Francesc E Borràs, Josep Lupón, Vicenta Llorente-Cortés, Antoni Bayes-Genis
Idiopathic dilated cardiomyopathy (IDCM) is a frequent cause of heart transplantation. Potentially valuable blood markers are being sought, and low-density lipoprotein receptor-related protein 1 (LRP1) has been linked to the underlying molecular basis of the disease. This study compared circulating levels of soluble LRP1 (sLRP1) in IDCM patients and healthy controls and elucidated whether sLRP1 is exported out of the myocardium through extracellular vesicles (EVs) to gain a better understanding of the pathogenesis of the disease...
May 29, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28552561/fxii-promotes-proteolytic-processing-of-the-lrp1-ectodomain
#20
Lukasz Wujak, Christina Hesse, Katherina Sewald, Danny Jonigk, Peter Braubach, Gregor Warnecke, Hans-Gerd Fieguth, Armin Braun, Günter Lochnit, Philipp Markart, Liliana Schaefer, Malgorzata Wygrecka
BACKGROUND: Factor XII (FXII) is a serine protease that is involved in activation of the intrinsic blood coagulation, the kallikrein-kinin system and the complement cascade. Although the binding of FXII to the cell surface has been demonstrated, the consequence of this event for proteolytic processing of membrane-anchored proteins has never been described. METHODS: The effect of FXII on the proteolytic processing of the low-density lipoprotein receptor-related protein 1 (LRP1) ectodomain was tested in human primary lung fibroblasts (hLF), alveolar macrophages (hAM) and in human precision cut lung slices (hPCLS)...
August 2017: Biochimica et Biophysica Acta
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