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Low density lipoprotein receptor related protein 1

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https://www.readbyqxmd.com/read/28516428/cerebrovascular-angiogenic-reprogramming-upon-lrp1-repression-impact-on-sphingosine-1-phosphate-mediated-signaling-in-brain-endothelial-cell-chemotactism
#1
Amélie Vézina, Cyndia Charfi, Alain Zgheib, Borhane Annabi
Switches in sphingolipid metabolism have recently been associated with oncogenic transformation, and a role for the low-density lipoprotein receptor-related protein 1 (LRP1) in sphingosine-1-phosphate (S1P) proangiogenic signaling inferred. S1P signaling crosstalk with LRP1 in brain microvascular endothelial cells (HBMEC) is however unclear. Transient in vitro siLRP1 gene silencing was compared to stable shLRP1 knockdown. We observed decreased expression of CCAAT/enhancer binding protein β (C/EBPβ), a transcription factor for which multiple binding sites are found within the promoter sequences of all five S1P receptor members, upon stable but not transient LRP1 repression...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28514532/the-dickkopf1-ckap4-axis-creates-a-novel-signaling-pathway-and-may-represent-a-molecular-target-for-cancer-therapy
#2
REVIEW
Akira Kikuchi, Katsumi Fumoto, Hirokazu Kimura
Dickkopf 1 (DKK1) is a secretory protein and antagonizes oncogenic Wnt signaling by binding to the Wnt co-receptor low-density lipoprotein receptor-related proteins 6 (LRP6). DKK1 is also suggested to regulate its own signaling to associate with tumor aggressiveness. However, the underlying mechanism by which DKK1 promotes cancer cell proliferation has remained to be clarified for a long time. It has been recently found that cytoskeleton-associated protein 4 (CKAP4), which was originally reported as an endoplasmic reticulum membrane protein, acts as a novel DKK1 receptor...
May 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28502511/functional-analysis-of-new-3-untranslated-regions-genetic-variants-in-genes-associated-with-genetic-hypercholesterolemias
#3
Flor María Pérez-Campo, Isabel De Castro-Orós, Alicia Noriega, Montserrat Cofán, Itziar Lamiquiz-Moneo, Ana Cenarro, Emilio Ros, Fernando Civeira, Miguel Pocoví, José Carlos Rodríguez-Rey
BACKGROUND: Familial hypercholesterolemia (FH) is the best-described autosomal dominant genetic hypercholesterolemia (GH). Mutations in candidate genes can explain a high proportion of FH cases, but for many, no causative mutations are detected (designed non-FG-GH), suggesting the existence of additional genetic variants associated with the disease. OBJECTIVE: We aimed to identify new single-nucleotide variants (SNVs) located at the 3' untranslated regions (3'UTRs) of the low-density lipoprotein receptor, low-density lipoprotein receptor-related protein-associated protein 1, ATP-binding cassette sub-family G member 5, and sterol regulatory element-binding protein 2 genes in non-FH-GH individuals and investigated whether the association of these SNVs with non-FH-GH could be explained by changes in the affinity of regulatory microRNAs (miRNA) targeting the sequences modified by the SNVs...
March 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28496400/lrp1-modulates-app-intraneuronal-transport-and-processing-in-its-monomeric-and-dimeric-state
#4
Uta-Mareike Herr, Paul Strecker, Steffen E Storck, Carolin Thomas, Verena Rabiej, Anne Junker, Sandra Schilling, Nadine Schmidt, C Marie Dowds, Simone Eggert, Claus U Pietrzik, Stefan Kins
The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP and affects its processing. This is assumed to be mostly caused by the impact of LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early in the secretory pathway was reported whereat retention of LRP1 in the ER leads to decreased APP cell surface levels and in turn, to reduced Aβ secretion. Here, we extended the biochemical and immunocytochemical analyses by showing via live cell imaging analyses in primary neurons that LRP1 and APP are transported only partly in common (one third) but to a higher degree in distinct fast axonal transport vesicles...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28495363/app-aplp2-and-lrp1-interact-with-pcsk9-but-are-not-required-for-pcsk9-mediated-degradation-of-the-ldlr-in-vivo
#5
Ting Fu, YangYang Guan, Junjie Xu, Yan Wang
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that post-transcriptionally regulates the levels of hepatic low-density lipoprotein receptors (LDLRs). PCSK9 binds to the extracellular domain of the LDLR, and the PCSK9-LDLR complex is internalized through canonical clathrin-dependent endocytosis and then delivered to lysosomes for degradation. The mechanism by which PCSK9 blocks recycling of the LDLR has not been fully defined. Previous reports showed that amyloid precursor-like protein 2 (APLP2) interacts with PCSK9, but its role in PCSK9-mediated LDLR degradation remains controversial...
May 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28487939/identification-of-novel-genes-associated-with-fracture-healing-in-osteoporosis-induced-by-krm2-overexpression-or-lrp5-deficiency
#6
Feng Gao, Feng Xu, Dankai Wu, Jieping Cheng, Peng Xia
The aim of the present study was to screen potential key genes associated with osteoporotic fracture healing. The microarray data from the Gene Expression Omnibus database accession number GSE51686, were downloaded and used to identify differentially expressed genes (DEGs) in fracture callus tissue samples obtained from the femora of type I collagen (Col1a1)‑kringle containing transmembrane protein 2 (Krm2) mice and low density lipoprotein receptor‑related protein 5‑/‑ (Lrp5‑/‑) transgenic mice of osteoporosis compared with those in wild‑type (WT) mice...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28482944/increased-birth-weight-is-associated-with-altered-gene-expression-in-neonatal-foreskin
#7
L J Reynolds, R I Pollack, R J Charnigo, C S Rashid, A J Stromberg, S Shen, J M O'Brien, K J Pearson
Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7) v...
May 9, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28473440/deficiency-of-lrp1-in-mature-adipocytes-promotes-diet-induced-inflammation-and-atherosclerosis
#8
Eddy S Konaniah, David G Kuhel, Joshua E Basford, Neal L Weintraub, David Y Hui
OBJECTIVE: Mice with adipocyte-specific inactivation of low-density lipoprotein receptor-related protein-1 (LRP1) are resistant to diet-induced obesity and hyperglycemia because of compensatory thermogenic response by muscle. However, the physiological function of LRP1 in mature adipocytes and its role in cardiovascular disease modulation are unknown. This study compared perivascular adipose tissues (PVAT) from wild-type (adLrp1(+/+) ) and adipocyte-specific LRP1 knockout (adLrp1(-/-)) mice in modulation of atherosclerosis progression...
May 4, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28464560/matriptase-induces-metalloproteinase-dependent-aggrecanolysis-in-vitro-and-in-vivo-multiple-mechanisms-promote-cartilage-damage-in-osteoarthritis
#9
David J Wilkinson, Angela Habgood, Heather K Lamb, Paul Thompson, Alastair R Hawkins, Antoine Désilets, Richard Leduc, Torsten Steinmetzer, Maya Hammami, Melody S Lee, Charles S Craik, Sharon Watson, Hua Lin, Jennifer M Milner, Andrew D Rowan
Objectives To assess the ability of the type II transmembrane serine proteinase matriptase to promote aggrecan loss from cartilage of osteoarthritis (OA) patients, and whether matriptase inhibition could prevent aggrecan loss and cartilage damage in experimental OA. Methods Aggrecan release was assessed from human OA cartilage explants and human stem cell-derived cartilage discs, whilst cartilage conditioned media were used for western blotting. Gene expression was analysed by real-time PCR. Murine OA was induced by surgical destabilisation of the medial meniscus, and matriptase inhibitors delivered via osmotic mini-pump or intra-articular injection...
May 2, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28447744/cyclic-compression-stimulates-osteoblast-differentiation-via-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway
#10
Xi Chen, Jianmin Guo, Yu Yuan, Zhongguang Sun, Binglin Chen, Xiaoyang Tong, Lingli Zhang, Chao Shen, Jun Zou
It is widely accepted that mechanical stress is an important factor in bone associated cell differentiation, including that of mesenchymal stem cells, osteoblasts and osteocytes. The present study aimed to determine the effect of mechanical cyclic compressive load on osteoblast differentiation, and whether this was associated with activation of the wingless‑type (Wnt)/β-catenin signaling pathway. Using a 3D scaffold model, MC3T3‑E1 cells were exposed to cyclic compressive loading via the Flexcell‑5000C™ Compression system...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28431990/a-common-polymorphism-decreases-lrp1-mrna-stability-and-is-associated-with-increased-plasma-factor-viii-levels
#11
Jiann-Der Lee, Kuang-Ming Hsiao, Pey-Jium Chang, Chih-Cheng Chen, Ya-Wen Kuo, Yen-Chu Huang, Huan-Lin Hsu, Ya-Hui Lin, Chih-Ying Wu, Ying-Chih Huang, Meng Lee, Chia-Yu Hsu, Yi-Ting Pan, Chih-Yu Kuo, Chun-Hsien Lin
The low-density lipoprotein receptor-related protein 1 (LRP1) gene is associated with increased levels of plasma factor VIII (FVIII). We aimed to explore eight functional genetic LRP1 variants for their potential roles in regulating FVIII levels and acute ischemic stroke (AIS). This genetic association study enrolled 192 patients with AIS and 134 controls. There were no significant differences in the genetic frequency of the eight functional single-nucleotide polymorphisms (SNPs) between the control and AIS groups...
April 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28425175/haemorrhagic-snake-venom-metalloproteases-and-human-adams-cleave-lrp5-6-which-disrupts-cell-cell-adhesions-in-vitro-and-induces-haemorrhage-in-vivo
#12
Tadahiko Seo, Taketo Sakon, Shiori Nakazawa, Asuka Nishioka, Kohei Watanabe, Kaori Matsumoto, Mari Akasaka, Narumi Shioi, Hitoshi Sawada, Satohiko Araki
Snake venom metalloproteases (SVMPs) are members of the a disintegrin and metalloprotease (ADAM) family of proteins, as they possess similar domains. SVMPs are known to elicit snake venom-induced haemorrhage; however, the target proteins and cleavage sites are not known. In this work, we identified a target protein of vascular apoptosis-inducing protein 1 (VAP1), an SVMP, relevant to its ability to induce haemorrhage. VAP1 disrupted cell-cell adhesions by relocating VE-cadherin and γ-catenin from the cell-cell junction to the cytosol, without inducing proteolysis of VE-cadherin...
April 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28418856/low-density-lipoprotein-receptor-related-protein-6-is-a-novel-coreceptor-of-protease-activated-receptor-2-in-the-dynamics-of-cancer-associated-%C3%AE-catenin-stabilization
#13
Jeetendra Kumar Nag, Arun Kancharla, Myriam Maoz, Hagit Turm, Daniel Agranovich, Chhedi Lal Gupta, Beatrice Uziely, Rachel Bar-Shavit
Protease-activated receptor-2 (PAR2) plays a central role in cancer; however, the molecular machinery of PAR2-instigated tumors remains to be elucidated. We show that PAR2 is a potent inducer of β-catenin stabilization, a core process in cancer biology, leading to its transcriptional activity. Novel association of low-density lipoprotein-related protein 6 (LRP6), a known coreceptor of Frizzleds (Fz), with PAR2 takes place following PAR2 activation. The association between PAR2 and LRP6 was demonstrated employing co-immunoprecipitation, bioluminescence resonance energy transfer (BRET), and confocal microscopy analysis...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417262/melatonin-inhibits-neural-cell-apoptosis-and-promotes-locomotor-recovery-via-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway-after-spinal-cord-injury
#14
Zhaoliang Shen, Zipeng Zhou, Shuang Gao, Yue Guo, Kai Gao, Haoyu Wang, Xiaoqian Dang
The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway...
April 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28411243/potent-vasoconstrictor-kisspeptin-10-induces-atherosclerotic-plaque-progression-and-instability-reversal-by-its-receptor-gpr54-antagonist
#15
Kengo Sato, Remina Shirai, Mina Hontani, Rina Shinooka, Akinori Hasegawa, Tomoki Kichise, Tomoyuki Yamashita, Hayami Yoshizawa, Rena Watanabe, Taka-Aki Matsuyama, Hatsue Ishibashi-Ueda, Shinji Koba, Youichi Kobayashi, Tsutomu Hirano, Takuya Watanabe
BACKGROUND: Kisspeptin-10 (KP-10), a potent vasoconstrictor and inhibitor of angiogenesis, and its receptor, GPR54, have currently received much attention in relation to pre-eclampsia. However, it still remains unknown whether KP-10 could affect atherogenesis. METHODS AND RESULTS: We evaluated the effects of KP-10 on human umbilical vein endothelial cells, human monocyte-derived macrophages, human aortic smooth muscle cells in vitro, and atherosclerotic lesions in apolipoprotein E-deficient (ApoE(-/-)) mice in vivo...
April 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28407763/klotho-ameliorates-oxidized-low-density-lipoprotein-ox-ldl-induced-oxidative-stress-via-regulating-lox-1-and-pi3k-akt-enos-pathways
#16
Yansheng Yao, Yanbing Wang, Yibo Zhang, Chang Liu
BACKGROUND: Atherosclerosis is a common cardiovascular disease that causes myocardial infarction, heart failure, and stroke. Increased oxidized low density lipoprotein (ox-LDL) in the sub-endothelium is the characteristic origin of atherogenesis. Klotho, an anti-aging protein, has been reported to protect against atherosclerosis and ameliorate endothelial dysfunction in vivo. The aim of this study is to investigatethe anti-oxidative activity of Klothoin ox-LDL-treated human umbilical vein endothelial cells (HUVECs)...
April 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28401370/the-research-on-the-relationship-of-rage-lrp-1-and-a%C3%AE-accumulation-in-the-hippocampus-prefrontal-lobe-and-amygdala-of-stz-induced-diabetic-rats
#17
Lou-Yan Ma, Yu-Lang Fei, Xiao-Ye Wang, Song-Di Wu, Jun-Hui Du, Mei Zhu, Long Jin, Ming Li, Hai-Long Li, Jia-Jia Zhai, Lu-Peng Ji, Ran-Ran Ma, Song-Fang Liu, Mo Li, Li Ma, Xiao-Rui Ma, Qiu-Min Qu, Ya-Li Lv
Diabetes mellitus (DM) has been regarded as an important risk factor for Alzheimer's disease (AD), and diabetic patients and animals have shown cognitive dysfunction. More research has shown that the amyloid-β (Aβ), which is a hallmark of AD, was found deposited in the hippocampus of diabetic rats. This Aβ accumulation is regulated by the receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein (LRP-1). However, the expression of RAGE and LRP-1 in diabetic rats is not very clear...
April 11, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28393867/endothelial-lrp1-regulates-metabolic-responses-by-acting-as-a-co-activator-of-ppar%C3%AE
#18
Hua Mao, Pamela Lockyer, Luge Li, Christie M Ballantyne, Cam Patterson, Liang Xie, Xinchun Pi
Low-density lipoprotein receptor-related protein 1 (LRP1) regulates lipid and glucose metabolism in liver and adipose tissue. It is also involved in central nervous system regulation of food intake and leptin signalling. Here we demonstrate that endothelial Lrp1 regulates systemic energy homeostasis. Mice with endothelial-specific Lrp1 deletion display improved glucose sensitivity and lipid profiles combined with increased oxygen consumption during high-fat-diet-induced obesity. We show that the intracellular domain of Lrp1 interacts with the nuclear receptor Pparγ, a central regulator of lipid and glucose metabolism, acting as its transcriptional co-activator in endothelial cells...
April 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28381441/role-of-lrp1-in-the-pathogenesis-of-alzheimer-s-disease-evidence-from-clinical-and-preclinical-studies
#19
Mitsuru Shinohara, Masaya Tachibana, Takahisa Kanekiyo, Guojun Bu
Among the low-density lipoprotein receptor (LDLR) family members, the roles of LDLR-related protein 1 (LRP1 or LRP) in the pathogenesis of Alzheimer's disease (AD), especially late-onset AD, have been the most studied by genetic, neuropathological and biomarker analyses (clinical studies) or cellular and animal model systems (preclinical studies) over the last 25 years. Although there are some conflicting reports, accumulating evidence from preclinical studies indicates that LRP1 not only regulates the metabolism of amyloid-β peptides (Aβ) in the brain and periphery, but also maintains brain homeostasis, impairment of which likely contributes to AD development in Aβ-independent manners...
April 4, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28378397/relationship-among-lrp1-expression-pyk2-phosphorylation-and-mmp-9-activation-in-left-ventricular-remodelling-after-myocardial-infarction
#20
Elena Revuelta-López, Carol Soler-Botija, Laura Nasarre, Aleyda Benitez-Amaro, David de Gonzalo-Calvo, Antoni Bayes-Genis, Vicenta Llorente-Cortés
Left ventricular (LV) remodelling after myocardial infarction (MI) is a crucial determinant of the clinical course of heart failure. Matrix metalloproteinase (MMP) activation is strongly associated with LV remodelling after MI. Elucidation of plasma membrane receptors related to the activation of specific MMPs is fundamental for treating adverse cardiac remodelling after MI. The aim of current investigation was to explore the potential association between the low-density lipoprotein receptor-related protein 1 (LRP1) and MMP-9 and MMP-2 spatiotemporal expression after MI...
April 4, 2017: Journal of Cellular and Molecular Medicine
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