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https://www.readbyqxmd.com/read/28990066/integrated-microarray-analysis-provided-novel-insights-to-the-pathogenesis-of-glaucoma
#1
Jinhui Wang, Daofei Qu, Jinghong An, Guoming Yuan, Yufu Liu
Glaucoma is characterized as a visual field defect, which is the second most common cause of blindness. The present study performed an integrated analysis of microarray studies of glaucoma derived from Gene Expression Omnibus (GEO). Following the identification of the differentially expressed genes (DEGs) in glaucoma compared with normal control (NC) tissues, the functional annotation, glaucoma‑specific protein‑protein interaction (PPI) network and transcriptional regulatory network constructions were performed...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27022195/raftlin-controls-lipopolysaccharide-induced-tlr4-internalization-and-ticam-1-signaling-in-a-cell-type-specific-manner
#2
Megumi Tatematsu, Ryuji Yoshida, Yuka Morioka, Noriko Ishii, Kenji Funami, Ayako Watanabe, Kazuko Saeki, Tsukasa Seya, Misako Matsumoto
The clathrin-dependent endocytic pathway is crucial for endosomal TLR3- and TLR4-mediated Toll-IL-1R domain-containing adaptor molecule-1 (TICAM-1) signaling. TLR4 uses a different signaling platform, plasma membrane and endosomes, for activation of TIRAP-MyD88 and TICAM-2-TICAM-1, respectively. LPS-induced endocytosis of TLR4 is mandatory for TICAM-1-mediated signaling including IFN-β production. Several molecules/mechanisms such as CD14, clathrin, and phosphatidylinositol metabolism have been reported to act as inducers of TLR4 translocation...
May 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/24524192/beyond-dsrna-toll-like-receptor-3-signalling-in-rna-induced-immune-responses
#3
REVIEW
Megumi Tatematsu, Tsukasa Seya, Misako Matsumoto
The innate immune system recognizes pathogen- and damage-associated molecular patterns using pattern-recognition receptors that activate a wide range of signalling cascades to maintain host homoeostasis against infection and inflammation. Endosomal TLR3 (Toll-like receptor 3), a type I transmembrane protein, senses RNAs derived from cells with viral infection or sterile tissue damage, leading to the induction of type I interferon and cytokine production, as well as dendritic cell maturation. It has been accepted that TLR3 recognizes perfect dsRNA, but little has been addressed experimentally with regard to the structural features of virus- or host-derived RNAs that activate TLR3...
March 1, 2014: Biochemical Journal
https://www.readbyqxmd.com/read/24317805/raftlin-a-new-biomarker-in-human-sepsis
#4
Wonhwa Lee, Hayoung Yoo, Sae-Kwang Ku, Shin-Woo Kim, Jong-Sup Bae
Raftlin is a major protein in lipid raft. The aim of this study was to evaluate blood levels of raftlin in septic patients. A prospective study of 82 patients with sepsis was conducted. Human umbilical vein endothelial cells (HUVECs) or mice were exposed to lipopolysaccharide (LPS, 100 ng/ml to HUVECs or 10 mg/kg to mice) or subjected to cecal ligation and puncture (CLP) surgery. Data showed that LPS induced upregulation of the synthesis and secretion of raftlin in LPS-treated HUVECs, and LPS-injected and CLP-mice...
June 2014: Inflammation
https://www.readbyqxmd.com/read/23911868/length-of-dsrna-poly-i-c-drives-distinct-innate-immune-responses-depending-on-the-cell-type
#5
M Firoz Mian, Amna N Ahmed, Mehrnaz Rad, Artem Babaian, Dawn Bowdish, Ali A Ashkar
Poly I:C, a synthetic dsRNA analogue, has been used extensively for decades to study innate responses in vivo and in different cell types. We have found substantial variability while using poly I:C from different sources. In this study we found that poly I:C from 2 commercial sources induced sharply opposite responses in myeloid and fibroblasts, depending on the length of the poly I:C. Although short poly I:C (≈ 1-1.5 kb) induced greater amounts of TNF-α, IL-8, and IFN-β and a stronger antiviral response in myeloid cells, it was a poor inducer in fibroblasts...
November 2013: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/23673618/toll-like-receptor-3-recognizes-incomplete-stem-structures-in-single-stranded-viral-rna
#6
Megumi Tatematsu, Fumiko Nishikawa, Tsukasa Seya, Misako Matsumoto
Endosomal Toll-like receptor 3 (TLR3) serves as a sensor of viral infection and sterile tissue necrosis. Although TLR3 recognizes double-stranded RNA, little is known about structural features of virus- or host-derived RNAs that activate TLR3 in infection/inflammatory states. Here we demonstrate that poliovirus-derived single-stranded RNA segments harbouring stem structures with bulge/internal loops are potent TLR3 agonists. Functional poliovirus-RNAs are resistant to degradation and efficiently induce interferon-α/β and proinflammatory cytokines in human and mouse cells in a TLR3-dependent manner...
2013: Nature Communications
https://www.readbyqxmd.com/read/22222511/interactive-effects-of-atoh7-and-rftn1-in-association-with-adult-onset-primary-open-angle-glaucoma
#7
COMPARATIVE STUDY
Jian-Huan Chen, Degui Wang, Chukai Huang, Yuqian Zheng, Haoyu Chen, Chi-Pui Pang, Mingzhi Zhang
PURPOSE: Genome-wide association studies have shown association of the atonal homolog 7 (ATOH7) and raftlin lipid raft linker 1 (RFTN1) genes with glaucoma-related optic disc parameters. ATOH7 and RFTN1 sequence variations were investigated in patients with primary open-angle glaucoma (POAG) and their relationships with vertical cup-to-disc ratio (VCDR) and central corneal thickness (CCT) were determined. METHODS: In 289 unrelated controls and 142 patients with adult-onset POAG, including 117 with high-tension glaucoma (HTG) and 25 with normal-tension glaucoma (NTG), the single exon of ATOH7 was sequenced by direct sequencing...
February 16, 2012: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/21402703/lowering-glycosphingolipid-levels-in-cd4-t-cells-attenuates-t-cell-receptor-signaling-cytokine-production-and-differentiation-to-the-th17-lineage
#8
Yunxiang Zhu, Nathan Gumlaw, Jozsef Karman, Hongmei Zhao, Jinhua Zhang, Ji-Lei Jiang, Pete Maniatis, Andrea Edling, Wei-Lien Chuang, Craig Siegel, James A Shayman, Johanne Kaplan, Canwen Jiang, Seng H Cheng
Lipid rafts reportedly have a role in coalescing key signaling molecules into the immunological synapse during T cell activation, thereby modulating T cell receptor (TCR) signaling activity. Recent findings suggest that a correlation may exist between increased levels of glycosphingolipids (GSLs) in the lipid rafts of T cells and a heightened response of those T cells toward activation. Here, we show that lowering the levels of GSLs in CD4(+) T cells using a potent inhibitor of glucosylceramide synthase (Genz-122346) led to a moderation of the T cell response toward activation...
April 29, 2011: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/21266579/raftlin-is-involved-in-the-nucleocapture-complex-to-induce-poly-i-c-mediated-tlr3-activation
#9
Ayako Watanabe, Megumi Tatematsu, Kazuko Saeki, Sachiko Shibata, Hiroaki Shime, Akihiko Yoshimura, Chikashi Obuse, Tsukasa Seya, Misako Matsumoto
The double-stranded RNA analog, poly(I:C), extracellularly activates both the endosomal Toll-like receptor (TLR) 3 and the cytoplasmic RNA helicase, melanoma differentiation-associated gene 5, leading to the production of type I interferons (IFNs) and inflammatory cytokines. The mechanism by which extracellular poly(I:C) is delivered to TLR3-positive organelles and the cytoplasm remains to be elucidated. Here, we show that the cytoplasmic lipid raft protein, Raftlin, is essential for poly(I:C) cellular uptake in human myeloid dendritic cells and epithelial cells...
March 25, 2011: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/19414744/a-major-lipid-raft-protein-raftlin-modulates-t-cell-receptor-signaling-and-enhances-th17-mediated-autoimmune-responses
#10
Kazuko Saeki, Satoru Fukuyama, Toranoshin Ayada, Mako Nakaya, Daisuke Aki, Giichi Takaesu, Toshikatsu Hanada, Yumiko Matsumura, Takashi Kobayashi, Ryusuke Nakagawa, Akihiko Yoshimura
The membrane microdomains known as lipid rafts have been shown to act as platforms for the initiation of various receptor signals. Through proteomic analysis, we have identified a novel protein termed Raftlin (raft-linking protein) as a major protein in lipid rafts. To determine the physiological and immunological functions of Raftlin in mammals, we generated Raftlin-deficient mice, as well as Raftlin-transgenic (Tg) mice. Although Raftlin was originally identified in B cells, we observe no severe abnormalities in the B cells of these mice, presumably due to a high expression of Raftlin-homologue (Raftlin-2)...
May 15, 2009: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/19346216/protein-profiling-of-plasma-membranes-defines-aberrant-signaling-pathways-in-mantle-cell-lymphoma
#11
Robert S Boyd, Rebekah Jukes-Jones, Renata Walewska, David Brown, Martin J S Dyer, Kelvin Cain
We used shotgun proteomics to identify plasma membrane and lipid raft proteins purified from B cells obtained from mantle cell lymphoma (MCL) patients in leukemic phase. Bioinformatics identified 111 transmembrane proteins, some of which were profiled in primary MCL cases, MCL-derived cell lines, and normal B cells using RT-PCR and Western blotting. Several transmembrane proteins, including CD27, CD70, and CD31 (PECAM-1), were overexpressed when compared with normal B cells. CD70 was up-regulated (>10-fold) in three of five MCL patients along with its cognate receptor CD27, which was up-regulated (4-9-fold) in five of five patients, suggesting that MCL cells may undergo autocrine stimulation via this signaling pathway...
July 2009: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/18164103/interactions-between-the-products-of-the-herpes-simplex-genome-and-alzheimer-s-disease-susceptibility-genes-relevance-to-pathological-signalling-cascades
#12
REVIEW
C J Carter
The products of the Herpes simplex (HSV-1) genome interact with many Alzheimer's disease susceptibility genes or proteins. These in turn affect those of the virus. For example, HSV-1 binds to heparan sulphate proteoglycans (HSPG2), or alpha-2-macroglobulin (A2M), and enters cells via nectin receptors, which are cleaved by gamma-secretase (APH1B, PSEN1, PSEN2, PEN2, NCSTN). The virus also binds to blood-borne lipoproteins and apolipoprotein E (APOE) is able to modify its infectivity. Viral uptake is cholesterol- and lipid raft-dependent (DHCR24, HMGCR, FDPS, RAFTLIN, SREBF1)...
May 2008: Neurochemistry International
https://www.readbyqxmd.com/read/17387528/association-study-of-cholesterol-related-genes-in-alzheimer-s-disease
#13
MULTICENTER STUDY
M Axel Wollmer, Kristel Sleegers, Martin Ingelsson, Cezary Zekanowski, Nathalie Brouwers, Aleksandra Maruszak, Fabienne Brunner, Kim-Dung Huynh, Lena Kilander, Rose-Marie Brundin, Marie Hedlund, Vilmantas Giedraitis, Anna Glaser, Sebastiaan Engelborghs, Peter P De Deyn, Elisabeth Kapaki, Magdalini Tsolaki, Makrina Daniilidou, Dimitra Molyva, George P Paraskevas, Dietmar R Thal, Maria Barcikowska, Jacek Kuznicki, Lars Lannfelt, Christine Van Broeckhoven, Roger M Nitsch, Christoph Hock, Andreas Papassotiropoulos
Alzheimer's disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD...
August 2007: Neurogenetics
https://www.readbyqxmd.com/read/12805216/the-b-cell-specific-major-raft-protein-raftlin-is-necessary-for-the-integrity-of-lipid-raft-and-bcr-signal-transduction
#14
Kazuko Saeki, Yoshiki Miura, Daisuke Aki, Tomohiro Kurosaki, Akihiko Yoshimura
Recent evidence indicates that membrane microdomains, termed lipid rafts, have a role in B-cell activation as platforms for B-cell antigen receptor (BCR) signal initiation. To gain an insight into the possible functioning of lipid rafts in B cells, we applied liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) methodologies to the identification of proteins that co-purified with lipid rafts of Raji cells. Among these raft proteins, we characterized a novel protein termed Raftlin (raft-linking protein)...
June 16, 2003: EMBO Journal
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