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Translocator protein

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https://www.readbyqxmd.com/read/28531892/emery-dreifuss-muscular-dystrophy-associated-mutant-forms-of-lamin-a-recruit-the-stress-responsive-protein-ankrd2-into-the-nucleus-affecting-the-cellular-response-to-oxidative-stress
#1
Silvia Angori, Cristina Capanni, Georgine Faulkner, Camilla Bean, Giuseppe Boriani, Giovanna Lattanzi, Vittoria Cenni
BACKGROUND: Ankrd2 is a stress responsive protein mainly expressed in muscle cells. Upon the application of oxidative stress, Ankrd2 translocates into the nucleus where it regulates the activity of genes involved in cellular response to stress. Emery-Dreifuss Muscular Dystrophy 2 (EDMD2) is a muscular disorder caused by mutations of the gene encoding lamin A, LMNA. As well as many phenotypic abnormalities, EDMD2 muscle cells also feature a permanent basal stress state, the underlying molecular mechanisms of which are currently unclear...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28530676/mutations-in-dzip1l-which-encodes-a-ciliary-transition-zone-protein-cause-autosomal-recessive-polycystic-kidney-disease
#2
Hao Lu, Maria C Rondón Galeano, Elisabeth Ott, Geraldine Kaeslin, P Jaya Kausalya, Carina Kramer, Nadina Ortiz-Brüchle, Nadescha Hilger, Vicki Metzis, Milan Hiersche, Shang Yew Tay, Robert Tunningley, Shubha Vij, Andrew D Courtney, Belinda Whittle, Elke Wühl, Udo Vester, Björn Hartleben, Steffen Neuber, Valeska Frank, Melissa H Little, Daniel Epting, Peter Papathanasiou, Andrew C Perkins, Graham D Wright, Walter Hunziker, Heon Yung Gee, Edgar A Otto, Klaus Zerres, Friedhelm Hildebrandt, Sudipto Roy, Carol Wicking, Carsten Bergmann
Autosomal recessive polycystic kidney disease (ARPKD), usually considered to be a genetically homogeneous disease caused by mutations in PKHD1, has been associated with ciliary dysfunction. Here, we describe mutations in DZIP1L, which encodes DAZ interacting protein 1-like, in patients with ARPKD. We further validated these findings through loss-of-function studies in mice and zebrafish. DZIP1L localizes to centrioles and to the distal ends of basal bodies, and interacts with septin2, a protein implicated in maintenance of the periciliary diffusion barrier at the ciliary transition zone...
May 22, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28530125/pro-inflammatory-activation-of-primary-microglia-and-macrophages-increases-18%C3%A2-kda-translocator-protein-expression-in-rodents-but-not-humans
#3
David R Owen, Nehal Narayan, Lisa Wells, Luke Healy, Erica Smyth, Eugenii A Rabiner, Dylan Galloway, John B Williams, Joshua Lehr, Harpreet Mandhair, Laura An Peferoen, Peter C Taylor, Sandra Amor, Jack P Antel, Paul M Matthews, Craig S Moore
The 18kDa Translocator Protein (TSPO) is the most commonly used tissue-specific marker of inflammation in positron emission tomography (PET) studies. It is expressed in myeloid cells such as microglia and macrophages, and in rodent myeloid cells expression increases with cellular activation. We assessed the effect of myeloid cell activation on TSPO gene expression in both primary human and rodent microglia and macrophages in vitro, and also measured TSPO radioligand binding with (3)H-PBR28 in primary human macrophages...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28529627/-18-f-ge-180-pet-detects-reduced-microglia-activation-after-lm11a-31-therapy-in-a-mouse-model-of-alzheimer-s-disease
#4
Michelle L James, Nadia P Belichenko, Adam J Shuhendler, Aileen Hoehne, Lauren E Andrews, Christina Condon, Thuy-Vi V Nguyen, Vladimer Reiser, Paul Jones, William Trigg, Jianghong Rao, Sanjiv S Gambhir, Frank M Longo
Microglial activation is a key pathological feature of Alzheimer's disease (AD). PET imaging of translocator protein 18 kDa (TSPO) is a strategy to detect microglial activation in vivo. Here we assessed flutriciclamide ([(18)F]GE-180), a new second-generation TSPO-PET radiotracer, for its ability to monitor response to LM11A-31, a novel AD therapeutic in clinical trials. AD mice displaying pathology were treated orally with LM11A-31 for 3 months. Subsequent [(18)F]GE-180-PET imaging revealed significantly lower signal in cortex and hippocampus of LM11A-31-treated AD mice compared to those treated with vehicle, corresponding with decreased levels of TSPO immunostaining and microglial Iba1 immunostaining...
2017: Theranostics
https://www.readbyqxmd.com/read/28529485/hydrostatin-sn1-a-sea-snake-derived-bioactive-peptide-reduces-inflammation-in-a-mouse-model-of-acute-lung-injury
#5
Guosheng Wu, Junjie Wang, Pengfei Luo, An Li, Song Tian, Hailong Jiang, Yongjun Zheng, Feng Zhu, Yiming Lu, Zhaofan Xia
Snake venom has been used for centuries as a traditional Chinese medicine. Hydrostatin-SN1 (H-SN1), a bioactive peptide extracted from the Hydrophis cyanocinctus venom gland T7 phage display library, was reported to have the ability to reduce inflammation in a dextran sulfate sodium-induced murine colitis model. In this study, we sought to investigate the inhibitory potential of H-SN1 on inflammation in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI), and elucidate the anti-inflammatory mechanism in LPS-stimulated RAW 264...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28529452/estradiol-suppresses-tlr4-triggered-apoptosis-of-decidual-stromal-cells-and-drives-an-anti-inflammatory-th2-shift-by-activating-sgk1
#6
Yiyun Lou, Minhao Hu, Qijing Wang, Mu Yuan, Ning Wang, Fang Le, Lejun Li, Shisi Huang, Liya Wang, Xiangrong Xu, Fan Jin
A pro-inflammatory cytokine profile at the feto-maternal interface may predispose immune maladaptation notably in early miscarriages. We investigated the involvement of estradiol (E2)-activated serum-glucocorticoid regulated kinase 1 (SGK1) in preserving the tolerogenic and pro-survival intrauterine microenvironment beneficial to gestation maintenance. Decidual SGK1 was down-regulated in early miscarriage, consistent with the lower serum E2 concentration seen in pregnancy loss. Lipopolysaccharide (LPS)/Toll-like receptors 4 (TLR4) signaling induced apoptosis and the pro-inflammatory T helper type (TH) 1 response of decidual stromal cells (DSCs) were associated with miscarriage...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28528355/increased-retinol-free-rbp4-contributes-to-insulin-resistance-in-gestational-diabetes-mellitus
#7
Yanmin Chen, Ping Lv, Mengkai Du, Zhaoxia Liang, Menglin Zhou, Danqing Chen
PURPOSE: Retinol-binding protein 4 (RBP4) is a circulating retinol transporter that is strongly associated with insulin resistance. The aim of this study was to evaluate the RBP4 and retinol level in rat model of gestational diabetes mellitus and the relationship between retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) and insulin resistance. METHODS: Pregnant rats were administered streptozotocin to induce diabetes. The RBP4 and retinol levels were evaluated in GDM and normal pregnant rats...
May 20, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28527955/neuroprotective-effect-of-the-alpha-7-nicotinic-receptor-agonist-pha-543613-in-an-in-vivo-excitotoxic-adult-rat-model
#8
Laura Foucault-Fruchard, Aurélie Doméné, Guylène Page, Marguerite Windsor, Patrick Emond, Nuno Rodrigues, Frédéric Dollé, Annelaure Damont, Frédéric Buron, Sylvain Routier, Sylvie Chalon, Daniel Antier
Neuroinflammation is a key component of the pathophysiology of neurodegenerative diseases. The link between nicotine intake and positive outcome has been established, suggesting a role played by nicotinic receptors (nAChRs), especially α7nAChRs. The objective of this study was to evaluate the potential dose effects of PHA 543613 on neuron survival and striatal microglial activation in a rat model of brain excitotoxicity. A preliminary study was performed in vitro to confirm PHA 543613 agonist properties on α7nAChRs...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28527857/novel-immunologic-approaches-to-melanoma-treatment
#9
I Escandell, J M Martín, E Jordá
Approaches to treating melanoma have changed radically since the introduction of immunotherapy, and survival figures are now higher than possible with earlier therapies. The immunomodulators currently available mainly block CTLA-4 (cytotoxicT lymphocyte-associated molecule-4) and PD-1 (programed cell death protein 1) translocated to the cell surface, where they inhibit the antitumor immune response. Treatments blocking these molecules are being more widely used. Research now seeks new molecular targets, the best combinations of available drugs, and biomarkers that can identify ideal candidates for each one...
May 17, 2017: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/28527256/-stat3-activation-by-hypoxia-in-in-vitro-models-of-cervix-cancer-and-endothelial-cells
#10
Óscar Ortega, Alejandro Ondo-Méndez, Ruth Garzón
INTRODUCTION: The biological behavior of cancer cells is influenced by the tumor microenvironment in which they develop. In this context, stressor stimuli such as hypoxia are considered critical for tumor development and therapeutic management. Cellular response to various stimuli is evidenced in the activation of intracellular signaling pathways such as JAK/STAT, which is one of the most important for its effects in differentiation and cell proliferation. OBJECTIVE: To evaluate the condition of the JAK/STAT pathway through the expression/activation of the STAT3 protein in cervix cancer cells (HeLa) and endothelial cells (EA...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28526927/sodium-thiosulphate-attenuates-brain-inflammation-induced-by-systemic-lipopolysaccharide-administration-in-c57bl-6j-mice
#11
Gonzalo Acero, Miryam Nava Catorce, Ricardo González-Mendoza, Marco Antonio Meraz-Rodríguez, Luis Fernando Hernández-Zimbron, Roberto González-Salinas, Goar Gevorkian
It has been demonstrated that peripheral infections accompanied by neuroinflammation may modify brain development or affect normal brain aging and represent major risk factors for the development of neurological disorders. A wide range of synthetic and natural compounds with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated for the first time that sodium thiosulphate (STS), a known antidote approved for treatment of certain medical conditions, is capable of reducing brain inflammation caused by systemic LPS administration...
May 19, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28526321/effects-of-dehp-and-its-metabolite-mehp-on-insulin-signalling-and-proteins-involved-in-glut4-translocation-in-cultured-l6-myotubes
#12
Mangala Priya Viswanathan, Vigneswari Mullainadhan, Mayilvanan Chinnaiyan, Balasubramanian Karundevi
Di-(2-ethylhexyl)phthalate (DEHP) is the plasticizer used in variety of medical and consumer products to impart structural flexibility. DEHP and its primary metabolite mono-(2-ethyl hexyl)phthalate (MEHP) posed a considerable interest because of their contribution to insulin resistance, type-2 diabetes and obesity. Experimental and epidemiological data have shown that DEHP affects blood glucose homeostasis. However, direct effect of DEHP and its metabolite MEHP on insulin signal transduction and glucose transporter 4 (GLUT4) translocation remain obscure...
May 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28525970/the-immunoregulatory-role-of-alpha-enolase-in-dendritic-cell-function-during-chlamydia-infection
#13
Khamia Ryans, Yusuf Omosun, Danielle N McKeithen, Tankya Simoneaux, Camilla C Mills, Nathan Bowen, Francis O Eko, Carolyn M Black, Joseph U Igietseme, Qing He
BACKGROUND: We have previously reported that interleukin-10 (IL-10) deficient dendritic cells (DCs) are potent antigen presenting cells that induced elevated protective immunity against Chlamydia. To further investigate the molecular and biochemical mechanism underlying the superior immunostimulatory property of IL-10 deficient DCs we performed proteomic analysis on protein profiles from Chlamydia-pulsed wild-type (WT) and IL-10(-/-) DCs to identify differentially expressed proteins with immunomodulatory properties...
May 19, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28525901/direct-inhibition-of-stat-signaling-by-platinum-drugs-contributes-to-their-anti-cancer-activity
#14
Stanleyson V Hato, Carl G Figdor, Susumu Takahashi, Anja E Pen, Altuna Halilovic, Kalijn F Bol, Angela Vasaturo, Yukie Inoue, Nienke de Haas, Dagmar Verweij, Carla M L Van Herpen, Johannes H Kaanders, Johan H J M van Krieken, Hanneke W M Van Laarhoven, Gerrit K J Hooijer, Cornelis J A Punt, Akira Asai, I Jolanda M de Vries, W Joost Lesterhuis
Platinum-based chemotherapeutics are amongst the most powerful anti-cancer drugs. Although their exact mechanism of action is not well understood, it is thought to be mediated through covalent DNA binding. We investigated the effect of platinum-based chemotherapeutics on signaling through signal transducer and activator of transcription (STAT) proteins, which are involved in many oncogenic signaling pathways. We performed in vitro experiments in various cancer cell lines, investigating the effects of platinum chemotherapeutics on STAT phosphorylation and nuclear translocation, the expression of STAT-modulating proteins and downstream signaling pathways...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525305/clinical-impact-of-the-cell-of-origin-classification-and-the-myc-bcl2-dual-expresser-status-in-diffuse-large-b-cell-lymphoma-treated-within-prospective-clinical-trials-of-the-german-high-grade-non-hodgkin-s-lymphoma-study-group
#15
Annette M Staiger, Marita Ziepert, Heike Horn, David W Scott, Thomas F E Barth, Heinz-Wolfram Bernd, Alfred C Feller, Wolfram Klapper, Monika Szczepanowski, Michael Hummel, Harald Stein, Dido Lenze, Martin-Leo Hansmann, Sylvia Hartmann, Peter Möller, Sergio Cogliatti, Georg Lenz, Lorenz Trümper, Markus Löffler, Norbert Schmitz, Michael Pfreundschuh, Andreas Rosenwald, German Ott
Purpose To explore the prognostic impact and interdependence of the cell-of-origin (COO) classification, dual expression (DE) of MYC and BCL2 proteins, and MYC, BCL2, and BCL6 translocations in two prospectively randomized clinical trials of patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Overall, 452 formalin-fixed paraffin-embedded samples from two prospective, randomized DLBCL trials (RICOVER-60, prospective, randomized study for patients > 60 years, all IPI groups; and R-MegaCHOEP, prospective, randomized study for patients ≤ 60 years with age-adjusted IPI 2,3) of the German High-Grade Non-Hodgkin Lymphoma Study Group were analyzed with the Lymph2Cx assay for COO classification, with immunohistochemistry for MYC and BCL2, and with fluorescent in situ hybridization for MYC, BCL2, and BCL6 rearrangements...
May 19, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28524723/l1-retrotransposition-is-activated-by-ten-eleven-translocation-protein-1-and-repressed-by-methyl-cpg-binding-proteins
#16
Peng Zhang, Anne K Ludwig, Florian D Hastert, Cathia Rausch, Anne Lehmkuhl, Ines Hellmann, Martha Smets, Heinrich Leonhardt, M Cristina Cardoso
One of the major functions of DNA methylation is the repression of transposable elements, such as the long-interspersed nuclear element 1 (L1). The underlying mechanism(s), however, are unclear. Here, we addressed how retrotransposon activation and mobilization are regulated by methyl-cytosine modifying ten-eleven-translocation (Tet) proteins and how this is modulated by methyl-CpG binding domain (MBD) proteins. We show that Tet1 activates both, endogenous and engineered L1 retrotransposons. Furthermore, we found that Mecp2 and Mbd2 repress Tet1-mediated activation of L1 by preventing 5hmC formation at the L1 promoter...
May 19, 2017: Nucleus
https://www.readbyqxmd.com/read/28523344/role-of-g3bp1-in-glucocorticoid-receptor-mediated-microrna-15b-and-microrna-23a-biogenesis-in-endothelial-cells
#17
Hoi-Hin Kwok, Po-Ying Poon, Kylie Hin-Man Mak, Lin-Yao Zhang, Pei Liu, Huoming Zhang, Nai-Ki Mak, Patrick Ying-Kit Yue, Ricky Ngok-Shun Wong
MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control of miRNA biogenesis by androgen and estrogen has been demonstrated, but the direct effects of the glucocorticoid receptor (GR) on miRNA biogenesis are unknown. This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells...
May 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28523272/structural-elements-regulating-aaa-protein-quality-control-machines
#18
REVIEW
Chiung-Wen Chang, Sukyeong Lee, Francis T F Tsai
Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28523069/crosstalk-between-aryl-hydrocarbon-receptor-and-glucocorticoid-receptor-in-human-retinal-pigment-epithelial-cells
#19
Hong Lan Jin, Yujin Choi, Kwang Won Jeong
The aryl hydrocarbon receptor (AHR) is known to mediate the cellular reaction involved in processing environmental contaminants and, ultimately, preventing accumulation of unfavorable extra lipids and proteins. Glucocorticoid receptor (GR) mediates the expression of genes associated with anti-inflammatory properties. Because AHR and GR are closely related in lipid metabolic dysregulation and inflammation, we speculate that AHR and GR may play a crucial role in AMD pathogenesis and focus on their crosstalk in human retinal pigment epithelial cells (ARPE-19)...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28523011/the-effects-of-herbicides-targeting-aromatic-and-branched-chain-amino-acid-biosynthesis-support-the-presence-of-functional-pathways-in-broomrape
#20
Evgenia Dor, Shmuel Galili, Evgeny Smirnov, Yael Hacham, Rachel Amir, Joseph Hershenhorn
It is not clear why herbicides targeting aromatic and branched-chain amino acid biosynthesis successfully control broomrapes-obligate parasitic plants that obtain all of their nutritional requirements, including amino acids, from the host. Our objective was to reveal the mode of action of imazapic and glyphosate in controlling the broomrape Phelipanche aegyptiaca and clarify if this obligatory parasite has its own machinery for the amino acids biosynthesis. P. aegyptiaca callus was studied to exclude the indirect influence of the herbicides on the parasite through the host plant...
2017: Frontiers in Plant Science
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