RT² Profiler PCR Array (96-Well Format and 384-Well [4 X 96] Format)
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Signalling Between Microvascular Endothelium and Cardiomyocytes Through Neuregulin Downloaded From
Cardiovascular Research (2014) 102, 194–204 SPOTLIGHT REVIEW doi:10.1093/cvr/cvu021 Signalling between microvascular endothelium and cardiomyocytes through neuregulin Downloaded from Emily M. Parodi and Bernhard Kuhn* Harvard Medical School, Boston Children’s Hospital, 300 Longwood Avenue, Enders Building, Room 1212, Brookline, MA 02115, USA Received 21 October 2013; revised 23 December 2013; accepted 10 January 2014; online publish-ahead-of-print 29 January 2014 http://cardiovascres.oxfordjournals.org/ Heterocellular communication in the heart is an important mechanism for matching circulatory demands with cardiac structure and function, and neuregulins (Nrgs) play an important role in transducing this signal between the hearts’ vasculature and musculature. Here, we review the current knowledge regarding Nrgs, explaining their roles in transducing signals between the heart’s microvasculature and cardiomyocytes. We highlight intriguing areas being investigated for developing new, Nrg-mediated strategies to heal the heart in acquired and congenital heart diseases, and note avenues for future research. ----------------------------------------------------------------------------------------------------------------------------------------------------------- Keywords Neuregulin Heart Heterocellular communication ErbB -----------------------------------------------------------------------------------------------------------------------------------------------------------† † † This article is part of the Spotlight Issue on: Heterocellular signalling -
The Epidermal Growth Factor Receptor Family As a Central Element for Cellular Signal Transduction and Diversification
Endocrine-Related Cancer (2001) 8 11–31 The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification N Prenzel, O M Fischer, S Streit, S Hart and A Ullrich Max-Planck Institut fu¨r Biochemie, Department of Molecular Biology, Am Klopferspitz 18A, 82152 Martinsried, Germany (Requests for offprints should be addressed to A Ullrich; Email: [email protected]) Abstract Homeostasis of multicellular organisms is critically dependent on the correct interpretation of the plethora of signals which cells are exposed to during their lifespan. Various soluble factors regulate the activation state of cellular receptors which are coupled to a complex signal transduction network that ultimately generates signals defining the required biological response. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases represents both key regulators of normal cellular development as well as critical players in a variety of pathophysiological phenomena. The aim of this review is to give a broad overview of signal transduction networks that are controlled by the EGFR superfamily of receptors in health and disease and its application for target-selective therapeutic intervention. Since the EGFR and HER2 were recently identified as critical players in the transduction of signals by a variety of cell surface receptors, such as G-protein-coupled receptors and integrins, our special focus is the mechanisms and significance of the interconnectivity between heterologous signalling systems. Endocrine-Related Cancer (2001) 8 11–31 Introduction autophosphorylation of cytoplasmic tyrosine residues (reviewed in Ullrich & Schlessinger 1990, Heldin 1995, Cell surface receptors integrate a multitude of extracellular Alroy & Yarden 1997). -
Involvement of CRH Receptors in the Neuroprotective Action of R-Apomorphine in the Striatal 6-OHDA Rat Model
Neuroscience & Medicine, 2013, 4, 299-318 299 Published Online December 2013 (http://www.scirp.org/journal/nm) http://dx.doi.org/10.4236/nm.2013.44044 Involvement of CRH Receptors in the Neuroprotective Action of R-Apomorphine in the Striatal 6-OHDA Rat Model Mustafa Varçin1, Eduard Bentea1, Steven Roosens1, Yvette Michotte1, Sophie Sarre1,2* 1Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Faculty of Medicine and Pharmacy, Brussels, Belgium; 2Belgian Pharmacists Association, Medicines Control Laboratory, Brussels, Belgium. Email: *[email protected] Received October 21st, 2013; revised November 20th, 2013; accepted December 10th, 2013 Copyright © 2013 Mustafa Varçin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT The dopamine D1-D2 receptor agonist, R-apomorphine, has been shown to be neuroprotective in different models of Parkinson’s disease. Different mechanisms of action for this effect have been proposed, but not verified in the striatal 6-hydroxydopamine rat model. In this study, the expression of a set of genes involved in 1) signaling, 2) growth and differentiation, 3) neuronal regeneration and survival, 4) apoptosis and 5) inflammation in the striatum was measured after a subchronic R-apomorphine treatment (10 mg/kg/day, subcutaneously, during 11 days) in the striatal 6-hydroxy- dopamine rat model. The expression of 84 genes was analysed by using the rat neurotrophins and receptors RT2 Pro- filer™ PCR array. The neuroprotective effects of R-apomorphine in the striatal 6-hydroxydopamine model were con- firmed by neurochemical and behavioural analysis. -
Regulation of Adipose Tissue Function and Metabolic Homeostasis
REGULATION OF ADIPOSE TISSUE FUNCTION AND METABOLIC HOMEOSTASIS by Guoxiao Wang A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Cellular and Molecular Biology) in the University of Michigan 2014 Doctoral committee: Associate Professor Jiandie D. Lin, Chair Associate Professor Peter Dempsey Professor Ormond MacDougald Professor Liangyou Rui Professor Alan R. Saltiel © Guoxiao Wang 2014 DEDICATION To my parents and my husband, for their unconditional love ii ACKNOWLEDGEMENTS I would like to give special thanks to my mentor Jiandie Lin, who inspires confidence, enhances criticism and drives me forward. He bears all the virtues of a good mentor, always available to students despite the tremendous demands on his time. By actively doing research himself, he led us from the front and served as a role model. He has created a lab that is scientifically intense yet nurturing. He celebrates everybody’s success and respects individual difference, allowing us to “smell the rose”. I also would like to thank Siming Li, senior research staff in our lab, who has provided tremendous help from the start of my rotation and throughout my thesis research. I want to thank all my labmates, for the help I receive and friendship I enjoy. Thank you Xuyun Zhao and Zhuoxian Meng for help on our collaborative projects. Thank you Zhimin Chen and Yuanyuan Xiao for sharing resources and ideas that moves my project forward. Thank you Zoharit Cozacov for being such a terrific technician. And thank you Qi Yu and Lin Wang for providing common reagents to allow the lab to run smoothly. -
New Insights Into the Secretory Functions of Brown Adipose Tissue
243 2 Journal of J Villarroya et al. Secretory functions of brown 243:2 R19–R27 Endocrinology adipose tissue REVIEW New insights into the secretory functions of brown adipose tissue Joan Villarroya, Rubén Cereijo, Aleix Gavaldà-Navarro, Marion Peyrou, Marta Giralt and Francesc Villarroya Departament de Bioquímica i Biomedicina Molecular and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain Correspondence should be addressed to F Villarroya: [email protected] Abstract In recent years, an important secretory role of brown adipose tissue (BAT) has emerged, Key Words which is consistent, to some extent, with the earlier recognition of the important f brown adipose tissue secretory role of white fat. The so-called brown adipokines or ‘batokines’ may play an f brown adipokine autocrine role, which may either be positive or negative, in the thermogenic function f batokine of brown adipocytes. Additionally, there is a growing recognition of the signalling f thermogenesis molecules released by brown adipocytes that target sympathetic nerve endings (such as neuregulin-4 and S100b protein), vascular cells (e.g., bone morphogenetic protein-8b), and immune cells (e.g., C-X-C motif chemokine ligand-14) to promote the tissue remodelling associated with the adaptive BAT recruitment in response to thermogenic stimuli. Moreover, existing indications of an endocrine role of BAT are being confirmed through the release of brown adipokines acting on other distant tissues and organs; a recent example is the recognition that BAT-secreted fibroblast growth factor-21 and myostatin target the heart and skeletal muscle, respectively. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
A Bioinformatics Model of Human Diseases on the Basis Of
SUPPLEMENTARY MATERIALS A Bioinformatics Model of Human Diseases on the basis of Differentially Expressed Genes (of Domestic versus Wild Animals) That Are Orthologs of Human Genes Associated with Reproductive-Potential Changes Vasiliev1,2 G, Chadaeva2 I, Rasskazov2 D, Ponomarenko2 P, Sharypova2 E, Drachkova2 I, Bogomolov2 A, Savinkova2 L, Ponomarenko2,* M, Kolchanov2 N, Osadchuk2 A, Oshchepkov2 D, Osadchuk2 L 1 Novosibirsk State University, Novosibirsk 630090, Russia; 2 Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia; * Correspondence: [email protected]. Tel.: +7 (383) 363-4963 ext. 1311 (M.P.) Supplementary data on effects of the human gene underexpression or overexpression under this study on the reproductive potential Table S1. Effects of underexpression or overexpression of the human genes under this study on the reproductive potential according to our estimates [1-5]. ↓ ↑ Human Deficit ( ) Excess ( ) # Gene NSNP Effect on reproductive potential [Reference] ♂♀ NSNP Effect on reproductive potential [Reference] ♂♀ 1 increased risks of preeclampsia as one of the most challenging 1 ACKR1 ← increased risk of atherosclerosis and other coronary artery disease [9] ← [3] problems of modern obstetrics [8] 1 within a model of human diseases using Adcyap1-knockout mice, 3 in a model of human health using transgenic mice overexpressing 2 ADCYAP1 ← → [4] decreased fertility [10] [4] Adcyap1 within only pancreatic β-cells, ameliorated diabetes [11] 2 within a model of human diseases -
Injury-Induced Upregulation of Bfgf and CNTF Mrnas in the Rat Retina
The Journal of Neuroscience, November 1995, 75(11): 7377-7385 Injury-Induced Upregulation of bFGF and CNTF mRNAS in the Rat Retina Rong Wen,1,2 Ying Song,1,2 Tong Cheng,ls2 Michael T. Matthes,2,3 Douglas Yasumura,2’3 Matthew M. LaVail;,s and Roy H. Steinbergi,2 Departments of ‘Physiology, 20phthalmology, and 3Anatomy, University of California, San Francisco, San Francisco, California 94143 Focal mechanical injury to the retina has been shown to sertion without injection, protects photoreceptors near the wound slow or prevent photoreceptor degeneration near the le- (Faktorovich et al., 1990; Silverman and Hughes, 1990; Blair et sion site in two animal models of retinal degeneration, in- al., 1991; Li et al., 1991). In constant light-induced photorecep- herited retinal dystrophy in the Royal College of Surgeons tor degeneration, a similar injury-dependent protection is ob- (RCS) and light damage in albino rats. Thus, when injured, served (Faktorovich et al., 1992). These findings imply that the the rat retina activates a self-protective mechanism to min- retina has a self-protective mechanism whose activation protects imize damage. To identify injury responsive factors and photoreceptors from damage and death. A similar self-protective cells, we examined the mFlNAs for the following factors mechanism appears to exist for retinal ganglion cells (Mansour- and some of their receptors: basic and acidic fibroblast Robey et al., 1994). growth factors (bFGF, aFGF) and FGF receptor-l (FGFRl); Several lines of evidence suggest that endogenous factors that ciliary neurotrophic factor (CNTF) and CNTF receptor (Y promote photoreceptor survival may be involved in this self- (CNTFRa); brain-derived neurotrophic factor (BDNF) and protective mechanism. -
Roles of Neuregulin1 in Neuromuscular Junction Development Jiajing Wang Wayne State University
Wayne State University Wayne State University Dissertations 1-2-2013 Roles Of Neuregulin1 In Neuromuscular Junction Development Jiajing Wang Wayne State University, Follow this and additional works at: http://digitalcommons.wayne.edu/oa_dissertations Recommended Citation Wang, Jiajing, "Roles Of Neuregulin1 In Neuromuscular Junction Development" (2013). Wayne State University Dissertations. Paper 807. This Open Access Dissertation is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Dissertations by an authorized administrator of DigitalCommons@WayneState. ROLES OF NEUREGULIN1 IN NEUROMUSCULAR JUNCTION DEVELOPMENT by JIAJING WANG DISSERTATION Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY 2013 MAJOR: MOLECULAR BIOLOGY AND GENETICS Approved by: ___________________________________ Advisor Date ___________________________________ ___________________________________ ___________________________________ © COPYRIGHT BY JIAJING WANG 2013 All Rights Reserved DEDICATION This work is dedicated to my parents, Bofang Wang and Liping Jin. It is their unconditional love, understanding, trust, and encouragement during all these years of study that motivates me to achieve my dream. Without their support, I would not be where I am. I owe my profound gratitude and deepest appreciation to them. ii ACKNOWLEDGEMENTS I would like to thank my advisor, Dr. Jeffrey Loeb, for giving me the opportunity to work on the spectrum of projects. Without his mentorship, guidance, and both optimism and criticism, the thesis would not have been completed. I would also like to thank my committee members, Dr. Gregory Kapatos, Dr. Alexander Gow, and Dr. Rodrigo Andrade for their invaluable comments and inputs. -
Adipocyte-Secreted Bmp8b Mediates Adrenergic-Induced Remodeling Of
ARTICLE DOI: 10.1038/s41467-018-07453-x OPEN Adipocyte-secreted BMP8b mediates adrenergic- induced remodeling of the neuro-vascular network in adipose tissue Vanessa Pellegrinelli1, Vivian J. Peirce1, Laura Howard2, Samuel Virtue1, Dénes Türei3,4,5, Martina Senzacqua6, Andrea Frontini 7, Jeffrey W. Dalley8,9, Antony R. Horton2, Guillaume Bidault1, Ilenia Severi 6, Andrew Whittle1, Kamal Rahmouni10, Julio Saez-Rodriguez 4,5, Saverio Cinti6, Alun M. Davies2 & Antonio Vidal-Puig1,11 1234567890():,; Activation of brown adipose tissue-mediated thermogenesis is a strategy for tackling obesity and promoting metabolic health. BMP8b is secreted by brown/beige adipocytes and enhances energy dissipation. Here we show that adipocyte-secreted BMP8b contributes to adrenergic-induced remodeling of the neuro-vascular network in adipose tissue (AT). Overexpression of bmp8b in AT enhances browning of the subcutaneous depot and maximal thermogenic capacity. Moreover, BMP8b-induced browning, increased sympathetic inner- vation and vascularization of AT were maintained at 28 °C, a condition of low adrenergic output. This reinforces the local trophic effect of BMP8b. Innervation and vascular remodeling effects required BMP8b signaling through the adipocytes to 1) secrete neuregulin-4 (NRG4), which promotes sympathetic axon growth and branching in vitro, and 2) induce a pro- angiogenic transcriptional and secretory profile that promotes vascular sprouting. Thus, BMP8b and NRG4 can be considered as interconnected regulators of neuro-vascular remodeling in AT and are potential therapeutic targets in obesity. 1 Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UK. 2 School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AT, UK. -
Nonalcoholic Fatty Liver Disease Progresses Into Severe NASH When Physiological Mechanisms of Tissue Homeostasis Collapse
182 Sookoian S, et al. , 2018; 17 (2): 182-186 OPINION March-April, Vol. 17 No. 2, 2018: 182-186 The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for Study of the Liver and the Canadian Association for the Study of the Liver Nonalcoholic Fatty Liver Disease Progresses into Severe NASH when Physiological Mechanisms of Tissue Homeostasis Collapse Silvia Sookoian,*,** Carlos J. Pirola*,*** * University of Buenos Aires, Institute of Medical Research A Lanari, Buenos Aires, Argentina. ** National Scientific and Technical Research Council (CONICET) - University of Buenos Aires, Institute of Medical Research (IDIM), Department of Clinical and Molecular Hepatology, Buenos Aires, Argentina. *** National Scientific and Technical Research Council (CONICET)-University of Buenos Aires, Institute of Medical Research (IDIM), Department of Molecular Genetics and Biology of Complex Diseases, Buenos Aires, Argentina. ABSTRACT Phenotypic modulation of NAFLD-severity by molecules derived from white (adipokines) and brown (batokines) adipose tissue may be important in inducing or protecting against the progression of the disease. Adipose tissue-derived factors can promote the pro- gression of NAFLD towards severe histological stages (NASH-fibrosis and NASHcirrhosis). This effect can be modulated by the release of adipokines or batokines that directly trigger an inflammatory response in the liver tissue or indirectly modulate related phenotypes, such as insulin resistance. Metabolically dysfunctional adipose tissue, which is often infiltrated by macrophages and crown-like histological structures, may also show impaired production of anti-inflammatory cytokines, which may favor NAFLD progression into aggressive phenotypes by preventing its protective effects on the liver tissue. Key words. NAFLD. NASH. Fibrosis. -
Akt-Mediated Survival of Oligodendrocytes Induced by Neuregulins
The Journal of Neuroscience, October 15, 2000, 20(20):7622–7630 Akt-Mediated Survival of Oligodendrocytes Induced by Neuregulins Ana I. Flores,1 Barbara S. Mallon,1 Takashi Matsui,2 Wataru Ogawa,3 Anthony Rosenzweig,2 Takashi Okamoto,1 and Wendy B. Macklin1 1Department of Neurosciences, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, 2Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02139, and 3Second Department of Internal Medicine, Kobe University School of Medicine, Chuo-ku, Kobe 650–0017, Japan Neuregulins have been implicated in a number of events in cells heregulin in glial cells, BAD was overexpressed in C6 glioma in the oligodendrocyte lineage, including enhanced survival, mi- cells. In these cells, heregulin induced phosphorylation of BAD at tosis, migration, and differentiation. At least two signaling path- Ser 136. Apoptosis of oligodendrocyte progenitor cells induced by ways have been shown to be involved in neuregulin signaling: the growth factor deprivation was effectively blocked by heregulin in phosphatidylinositol (PI)-3 kinase and the mitogen-activated pro- a wortmannin-sensitive manner. Overexpression of dominant tein kinase pathways. In the present studies, we examined the negative Akt but not of wild-type Akt by adenoviral gene transfer signaling pathway involved in the survival function of heregulin, in primary cultures of both oligodendrocytes and their progeni- focusing on heregulin-induced changes in Akt activity