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Low density lipoprotein receptor related protein 1

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https://www.readbyqxmd.com/read/28332354/cyclized-oligopeptide-targeting-lrp5-6-dkk1-interaction-reduces-the-growth-of-tumor-burden-in-a-multiple-myeloma-mouse-model
#1
Bo Mi Park, Eun Jin Kim, Hee Jin Nam, Dongdong Zhang, Chu Hyun Bae, Myeongmo Kang, Heeyoun Kim, Weontae Lee, Bjarne Bogen, Sung Kil Lim
PURPOSE: Dickkopf 1 (DKK1) has been extensively investigated in mouse models of multiple myeloma, which results in osteolytic bone lesions. Elevated DKK1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Present pharmaceutical approaches to target bone lesions are limited to antiresorptive agents. In this study, we developed a cyclized oligopeptide against DKK1-low density lipoprotein receptor-related protein (LRP) 5/6 interaction and tested the effects of the oligopeptide on tumor burden...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28330861/clearing-the-way-to-a-healthy-brain
#2
Jill Morris
Astrocytic low-density lipoprotein receptor-related protein 1 is a key player in β-amyloid clearance.
March 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28316179/-effects-and-related-mechanism-of-angiotensin-1-7-on-toll-like-receptor-4-mediated-oxidative-stress-in-human-umbilical-vein-endothelial-cells
#3
W F Yan, J J Xue, H Y Yang, B Liang, Z M Yang
Objective: To explore the role and related mechanisms of angiotensin-(1-7)(Ang-(1-7)) on Toll-like receptor 4 (TLR4) mediated oxidized low-density lipoprotein(ox-LDL)-induced oxidative stress in human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were cultured in vitro and divided into six groups: the control group (normal medium), the ox-LDL group(treated with 75 mg/L ox-LDL), the ox-LDL+ Ang-(1-7) group (1 μmol/L Ang-(1-7) pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL), the ox-LDL+ Ang-(1-7)+ A-779 group(1 μmol/L A-779 (Mas receptor) pretreated for 30 minutes, 1 μmol/L Ang-(1-7) pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL), the ox-LDL+ A-779 group (1 μmol/L A-779 pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL), the ox-LDL+ HTA125 group (10 μg/L HTA125 (TLR4-blocking antibody) pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL )...
March 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28304302/sleep-deprivation-induced-plasma-amyloid-%C3%AE-transport-disturbance-in-healthy-young-adults
#4
Meng Wei, Beiyu Zhao, Kang Huo, Yongning Deng, Suhang Shang, Jie Liu, Yanbo Li, Louyan Ma, Yu Jiang, Liangjun Dang, Chen Chen, Shan Wei, Juanli Zhang, Hailei Yang, Fan Gao, Qiumin Qu
BACKGROUND: Sleep is an important physiological process and beneficial in the removal of brain metabolites and functional recovery. Prior studies have shown that sleep disorders are significant risk factors for Alzheimer's disease (AD). OBJECTIVE: The present study was designed to characterize the effect of short-term total sleep deprivation (TSD) on plasma amyloid-β (Aβ) concentrations. METHODS: A clinical trial was conducted between March 1, 2016, and April 1, 2016...
March 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28303501/isoflurane-postconditioning-inhibits-tpa-induced-matrix-metalloproteinases-activation-after-hypoxic-injury-via-low-density-lipoprotein-receptor-related-protein-and-extracellular-signal-regulated-kinase-pathway
#5
So Yeon Kim, So Yeong Cheon, Eun Jung Kim, Jae Hoon Lee, Eun Hee Kam, Jeong Min Kim, Miran Park, Bon-Nyeo Koo
Tissue plasminogen activator (tPA) is the only recommended pharmacological treatment for acute ischemic stroke. However, tPA can induce intracerebral hemorrhage by blood-brain barrier breakdown through an increase in matrix metalloproteinases (MMPs). Previously, we showed that isoflurane postconditioning reduced intracranial hemorrhage following tPA treatment after cerebral ischemia. Here, we investigated the mechanism by which isoflurane postconditioning reduces tPA-induced MMP-2 and MMP-9 activation following hypoxia/reoxygenation (H/R) in brain endothelial cells...
March 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28301372/news-on-the-molecular-regulation-and-function-of-hepatic-low-density-lipoprotein-receptor-and-ldlr-related-protein-1
#6
Bart van de Sluis, Melinde Wijers, Joachim Herz
PURPOSE OF REVIEW: Clearing of atherogenic lipoprotein particles by the liver requires hepatic low-density lipoprotein receptor (LDLR) and LDLR-related protein 1 (LRP1). This review highlights recent studies that have expanded our understanding of the molecular regulation and metabolic functions of LDLR and LRP1 in the liver. RECENT FINDINGS: Various proteins orchestrate the intracellular trafficking of LDLR and LRP1. After internalization, the receptors are redirected via recycling endosomes to the cell surface...
March 15, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28300459/mildly-elevated-unconjugated-bilirubin-is-associated-with-reduced-platelet-activation-related-thrombogenesis-and-inflammation-in-gilbert-s-syndrome
#7
Avinash R Kundur, Abishek B Santhakumar, Andrew C Bulmer, Indu Singh
Gilbert's syndrome (GS) is associated with a mild unconjugated hyperbilirubinemia, increased circulating antioxidant capacity, and reduced cardiovascular disease (CVD) risk. The current study investigated whether mildly elevated circulating unconjugated bilirubin (UCB) is negatively associated with multiple thrombotic risk factors including platelet activity, hemostatic function, and inflammation in individuals with GS. Blood samples were collected from matched GS and control subjects (14 per group). Activation-dependent platelet surface marker expression of PAC-1 (binds to GPIIb/IIIa surface receptors on activated platelets) and CD62P (marker for P-selectin released from activated degranulated platelets) was assessed in adenosine diphosphate (ADP)-stimulated platelets using flow cytometry...
March 16, 2017: Platelets
https://www.readbyqxmd.com/read/28294375/identification-of-the-interaction-between-bta-mir-370-and-olr1-gene-in-bovine-adipocyte
#8
H F Li, S H Wang, Y Guo, H B Zhao, X Y Li, X Wang
It has been shown that the oxidized low density lipoprotein receptor 1 (OLR1) gene plays an important role in the degradation of oxidized low density lipoprotein. Previous studies found a SNP in the 3'-untranslated region (3'-UTR) of the OLR1 gene associated with milk production traits in different dairy cattle populations and with loin eye area and marbling depth in beef cattle. MicroRNAs can regulate gene expression by binding the 3'-UTR of target genes to degrade or to repress the translation of target genes...
March 10, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28283687/impact-of-gain-of-function-mutations-in-the-low-density-lipoprotein-receptor-related-protein-5-lrp5-on-glucose-and-lipid-homeostasis
#9
D Foer, M Zhu, R L Cardone, C Simpson, R Sullivan, S Nemiroff, G Lee, R G Kibbey, K F Petersen, K L Insogna
LRP5 loss-of-function mutations have been shown to cause profound osteoporosis and have been associated with impaired insulin sensitivity and dysregulated lipid metabolism. We hypothesized that gain-of-function mutations in LRP5 would also affect these parameters. We therefore studied individuals with LRP5 gain-of-function mutations exhibiting high bone mass (HBM) phenotypes and found that while there was no detected change in insulin sensitivity, there was a significant reduction in serum LDL. INTRODUCTION: Wnt signaling through LRP5 represents a newly appreciated metabolic pathway, which potentially represents a target for drug discovery in type 2 diabetes and hyperlipidemia...
March 10, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28275161/astrocytic-lrp1-mediates-brain-a%C3%AE-clearance-and-impacts-amyloid-deposition
#10
Chia-Chen Liu, Jin Hu, Na Zhao, Jian Wang, Wang Na, John R Cirrito, Takahisa Kanekiyo, David M Holtzman, Guojun Bu
Accumulation and deposition of amyloid-β (Aβ) in the brain represents an early and perhaps necessary step in the pathogenesis of Alzheimer's disease (AD). Aβ accumulation leads to the formation of Aβ aggregates which may directly and indirectly lead to eventual neurodegeneration. While Aβ production is accelerated in many familial forms of early-onset AD, increasing evidence indicates that impaired clearance of Aβ is more evident in late-onset AD. To uncover the mechanisms underlying impaired Aβ clearance in AD, we examined the role of low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28274609/tongxinluo-improves-the-cognition-by-reducing-%C3%AE-amyloid-accumulation-in-spontaneous-hypertensive-rats
#11
Yu-Lang Fei, Hong-Jun Lv, Yan-Bo Li, Jie Liu, Yi-Hua Qian, Wei-Na Yang, Kai-Ge Ma, Hong-Bao Li, Qiu-Min Qu
β-amyloid (Aβ) accumulation in the brain is the major pathophysiology of Alzheimer disease (AD). Hypertension is a risk factor for AD by promoting Aβ deposition. Traditional Chinese medicinal compound tongxinluo (TXL) can improve blood circulation and endothelium-dependent vasodilation. This study investigates the effects of TXL on cognition and Aβ accumulation using spontaneously hypertensive rats (SHRs). TXL was intragastrically administered to SHRs at low-dose, mid-dose and high-dose for 15, 30 or 60 days...
March 5, 2017: Brain Research
https://www.readbyqxmd.com/read/28263310/deficiency-of-the-hepatokine-selenoprotein-p-increases-responsiveness-to-exercise-in-mice-through-upregulation-of-reactive-oxygen-species-and-amp-activated-protein-kinase-in-muscle
#12
Hirofumi Misu, Hiroaki Takayama, Yoshiro Saito, Yuichiro Mita, Akihiro Kikuchi, Kiyo-Aki Ishii, Keita Chikamoto, Takehiro Kanamori, Natsumi Tajima, Fei Lan, Yumie Takeshita, Masao Honda, Mutsumi Tanaka, Seiji Kato, Naoto Matsuyama, Yuya Yoshioka, Kaito Iwayama, Kumpei Tokuyama, Nobuhiko Akazawa, Seiji Maeda, Kazuhiro Takekoshi, Seiichi Matsugo, Noriko Noguchi, Shuichi Kaneko, Toshinari Takamura
Exercise has numerous health-promoting effects in humans; however, individual responsiveness to exercise with regard to endurance or metabolic health differs markedly. This 'exercise resistance' is considered to be congenital, with no evident acquired causative factors. Here we show that the anti-oxidative hepatokine selenoprotein P (SeP) causes exercise resistance through its muscle receptor low-density lipoprotein receptor-related protein 1 (LRP1). SeP-deficient mice showed a 'super-endurance' phenotype after exercise training, as well as enhanced reactive oxygen species (ROS) production, AMP-activated protein kinase (AMPK) phosphorylation and peroxisome proliferative activated receptor γ coactivator (Ppargc)-1α (also known as PGC-1α; encoded by Ppargc1a) expression in skeletal muscle...
February 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28258256/decreased-adiponectin-mediated-signaling-through-the-adipor2-pathway-is-associated-with-carotid-plaque-instability
#13
Karina Gasbarrino, Huaien Zheng, Anouar Hafiane, John P Veinot, Chi Lai, Stella S Daskalopoulou
BACKGROUND AND PURPOSE: Adiponectin, the most abundantly secreted anti-inflammatory adipokine, protects against all stages of atherosclerotic plaque formation by acting on its receptors, AdipoR1 (adiponectin receptor 1) and AdipoR2 (adiponectin receptor 2). Through binding of AdipoR1, adiponectin leads to the activation of the AMPK (adenosine monophosphate-activated protein kinase) pathway, whereas stimulation of PPAR-α (peroxisome proliferator-activated receptor-α) is attributed to the binding of AdipoR2...
March 3, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28256585/lrp1-influences-trafficking-of-n-type-calcium-channels-via-interaction-with-the-auxiliary-%C3%AE-2%C3%AE-1-subunit
#14
Ivan Kadurin, Simon W Rothwell, Beatrice Lana, Manuela Nieto-Rostro, Annette C Dolphin
Voltage-gated Ca(2+) (CaV) channels consist of a pore-forming α1 subunit, which determines the main functional and pharmacological attributes of the channel. The CaV1 and CaV2 channels are associated with auxiliary β- and α2δ-subunits. The molecular mechanisms involved in α2δ subunit trafficking, and the effect of α2δ subunits on trafficking calcium channel complexes remain poorly understood. Here we show that α2δ-1 is a ligand for the Low Density Lipoprotein (LDL) Receptor-related Protein-1 (LRP1), a multifunctional receptor which mediates trafficking of cargoes...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228716/intranasal-bmp9-ameliorates-alzheimer-disease-like-pathology-and-cognitive-deficits-in-app-ps1-transgenic-mice
#15
Zigao Wang, Lu Xiong, Wenbin Wan, Lijie Duan, Xiaojing Bai, Hengbing Zu
Alzheimer's disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28222408/severe-osteoporosis-with-multiple-spontaneous-vertebral-fractures-in-a-young-male-carrying-triple-polymorphisms-in-the-vitamin-d-receptor-collagen-type-1-and-low-density-lipoprotein-receptor-related-peptide-5-genes
#16
Maria P Yavropoulou, Panagoulia Kollia, Dimitris Chatzidimitriou, Stavroula Samara, Lemonia Skoura, John G Yovos
Osteoporosis is a common disease with a strong genetic component. Several studies have reported the vitamin D receptor (VDR), collagen type I (COL1A1), and LDL receptor-related protein 5 (LRP5) genes as the most likely candidates. However, most of the studies have been carried out in postmenopausal women and older men and show inconsistent results. CASE PRESENTATION: We report a case of a 26-year old male who presented with severe back pain of acute onset, unrelated to any kind of trauma, and diffuse myalgia...
October 2016: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28167099/27-hydroxycholesterol-regulates-cholesterol-synthesis-and-transport-in-c6-glioma-cells
#17
Yu An, Dan-Di Zhang, Huan-Ling Yu, Wei-Wei Ma, Yan-Hui Lu, Quan-Ri Liu, Rong Xiao
The oxysterol 27-Hydroxycholesterol (27-OHC) is a major cholesterol metabolite that can cross the blood brain barrier (BBB) from peripheral circulation to the brain. Currently, the role of 27-OHC on cholesterol homeostasis in astrocytes and the underlying mechanisms are not defined. Since all brain cholesterol is essentially synthesized in brain itself and astrocytes as net producers of cholesterol are essential for normal brain function, here we investigated the effects of 27-OHC on cholesterol synthesis and transport in C6 glioma cells...
February 3, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28158288/mir-375-3p-negatively-regulates-osteogenesis-by-targeting-and-decreasing-the-expression-levels-of-lrp5-and-%C3%AE-catenin
#18
Tianhao Sun, Chen-Tian Li, Lifeng Xiong, Ziyu Ning, Frankie Leung, Songlin Peng, William W Lu
Wnt signaling pathways are essential for bone formation. Previous studies showed that Wnt signaling pathways were regulated by miR-375. Thus, we aim to explore whether miR-375 could affect osteogenesis. In the present study, we investigated the roles of miR-375 and its downstream targets. Firstly, we revealed that miR-375-3p negatively modulated osteogenesis by suppressing positive regulators of osteogenesis and promoting negative regulators of osteogenesis. In addition, the results of TUNEL cell apoptosis assay showed that miR-375-3p induced MC3T3-E1 cell apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28151034/sfrp3-and-dkk1-regulate-fibroblast-like-synoviocytes-markers-and-wnt-elements-expression-depending-on-cellular-context
#19
Dorra Elhaj Mahmoud, Nadia Sassi, Ghassen Drissi, Maher Barsaoui, Khaled Zitouna, Hela Sahli, Maryam Kallel-Sellami, Lassad Kanoun, Elhem Cheour, Lilia Laadhar
CONTEXT: Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) display pathogenic behavior. Various members of the Wnt pathway, especially the canonical Wnt/β-catenin cascade, may contribute to autonomous RA FLS activation. It has been shown that the two Wnt inhibitors: sFRP3 and DKK1 contribute to several critical aspects of joint biology. However, their effects on RA FLS are poorly characterized. The aim of our study was to investigate the effects of sFRP3 and DKK1 on FLS markers, Wnt components, and target oncogenes expression by RA FLS and compare the findings to osteoarthritic (OA) FLS...
February 2, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28143772/stearoyl-coa-desaturase-promotes-liver-fibrosis-and-tumor-development-in-mice-via-a-wnt-positive-signaling-loop-by-stabilization-of-low-density-lipoprotein-receptor-related-proteins-5-and-6
#20
Keane K Y Lai, Soo-Mi Kweon, Feng Chi, Edward Hwang, Yasuaki Kabe, Reiichi Higashiyama, Lan Qin, Rui Yan, Raymond P Wu, Naoaki Fujii, Samuel French, Jun Xu, Jian-Ying Wang, Ramanchadran Murali, Lopa Mishra, Ju-Seog Lee, James M Ntambi, Hidekazu Tsukamoto
BACKGROUND & AIMS: Stearoyl-CoA desaturase (SCD) synthesizes monounsaturated fatty acids (MUFAs) and has been associated with development of metabolic syndrome, tumorigenesis, and stem cell characteristics. We investigated whether and how SCD promotes liver fibrosis and tumor development in mice. METHODS: Rodent primary hepatic stellate cells (HSCs), mouse liver tumor-initiating stem cell-like cells (TICs), and human hepatocellular carcinoma (HCC) cell lines were exposed to Wnt signaling inhibitors and changes in gene expression patterns were analyzed...
January 29, 2017: Gastroenterology
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