DOCSLIB.ORG

Glial Protein S100B Modulates Long-Term Neuronal Synaptic Plasticity

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Glial Protein S100B Modulates Long-Term Neuronal Synaptic Plasticity Glial protein S100B modulates long-term neuronal synaptic plasticity Hiroshi Nishiyama*†, Thomas Kno¨ pfel†, Shogo Endo‡, and Shigeyoshi Itohara*§ *Laboratories for Behavioral Genetics and †Neuronal Circuit Dynamics, and ‡Neuronal Circuit Mechanisms Research Group, Brain Science Institute (BSI), Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan Communicated by Richard F. Thompson, University of Southern California, Los Angeles, CA, January 11, 2002 (received for review August 1, 2001) Glial cells are traditionally regarded as elements for structural subject of debate (1). Transgenic mice overexpressing human support and ionic homeostasis, but have recently attracted atten- S100B exhibit impaired hippocampal LTP and spatial learning tion as putative integral elements of the machinery involved in (11). Transgenic mice overexpressing S100B might not be ap- synaptic transmission and plasticity. Here, we demonstrate that propriate for evaluating the physiological roles of S100B, how- calcium-binding protein S100B, which is synthesized in consider- ever, because overexpression of S100B partly mimics patholog- able amounts in astrocytes (a major glial cell subtype), modulates ical conditions in some neuronal diseases, such as Down’s long-term synaptic plasticity. Mutant mice devoid of S100B devel- syndrome and Alzheimer’s disease (12, 13). The constitutive oped normally and had no detectable abnormalities in the cyto- overexpression of S100B might cause chronic neuronal damage architecture of the brain. These mutant mice, however, had (14, 15). Thus, there is no clear consensus regarding the signif- strengthened synaptic plasticity as identified by enhanced long- icance of this glial protein in neuronal synaptic plasticity. term potentiation (LTP) in the hippocampal CA1 region. Perfusion To clarify the precise role of S100B in neuronal synaptic of hippocampal slices with recombinant S100B proteins reversed plasticity, we generated mice devoid of S100B by using gene the levels of LTP in the mutant slices to those of the wild-type slices, targeting methods. We here demonstrate that the deletion of indicating that S100B might act extracellularly. In addition to S100B enhances hippocampal synaptic plasticity and hippocam- enhanced LTP, mutant mice had enhanced spatial memory in the pus-dependent learning and memory. Morris water maze test and enhanced fear memory in the contex- tual fear conditioning. The results indicate that S100B is a glial Materials and Methods modulator of neuronal synaptic plasticity and strengthen the Generation of S100B-Null Mice. All experimental protocols were notion that glial–neuronal interaction is important for information approved by the RIKEN Institutional Animal Care and Use processing in the brain. Committee. A genomic clone of the murine S100b gene was isolated from 129͞sv genomic DNA ␭FIXII library (Stratagene). everal lines of evidence suggest that glial cells play an active A 3.5-kb SpeI–HindIII fragment including the entire S100b Srole in excitatory neurotransmission in the central nervous coding sequence was replaced by a neomycin selection marker, system (1, 2). For instance, astrocytes can release glutamate in loxP-pgk-neo-loxP cassette. A 1.1-kb MC1-DT-A cassette, a Ј response to physiological increases in their intracellular calcium negative selection marker, was added at the 3 end of the concentration, and then evoke substantial glutamatergic cur- targeting vector. The E14 embryonic stem cell line was used for rents in neighboring neurons (3). Oligodendrocyte precursor gene targeting. Homologous recombinant clones were injected ͞ cells directly receive glutamatergic inputs from hippocampal into mouse C57BL 6J blastocysts. Male chimeras were mated ͞ pyramidal neurons (4). These findings, together with earlier with C57BL 6J females to obtain the heterozygous mice. The ͞ studies showing that glial cells express many types of neuro- heterozygotes were further crossbred with C57BL 6J mice five transmitter receptors and respond to neurotransmitter by gen- to seven times, and the resultant heterozygotes were interbred to erating slowly propagating calcium waves (5), suggest that glial– obtain the wild-type and homozygous mice that were used in the neuronal reciprocal signaling may play a role in synaptic present study. Genotypes were determined by Southern blot ͞ Ј plasticity and eventually in information processing in the brain. and or PCR. PCR primers used were GTF1 (5 -GAGACGCT- Ј Ј Indeed, this notion has been supported by the findings that the GGACGAAGATGG-3 ), GTF2 (5 -CTTGACGAGTTCT- Ј Ј mice devoid of glial fibrillary acidic protein (GFAP: an inter- TCTGAGG-3 ), and SR1 (5 -CTGGGAAGGGTTGGGGTT- Ј mediate filament specific to astrocytes) showed enhanced long- TCA-3 ). GTF1 and SR1 yield 280-bp fragments from the term potentiation (LTP) in the hippocampal CA1 region and wild-type allele, and GTF2 and SR1 yield 160-bp fragments from decreased long-term depression in the cerebellum associated the mutant allele. with impaired eye-blink conditioning (6, 7). However, the mo- ␮ lecular mechanism underlying glial–neuronal interactions is Northern Blotting. Total RNA (20 g) from mouse brain was poorly understood. electrophoresed on formaldehyde agarose gels and transferred ϩ One of the candidates that might be involved in glia-to-neuron to Hybond N filter (Amersham Pharmacia). The filter was 32 signaling is the calcium-binding protein S100B. S100B is a hybridized with P- labeled 280 bp cDNA probe containing the member of the S100 family of proteins containing two EF-hand- entire S100b coding sequence. type calcium-binding domains (8). The highest level of expres- Histological Analysis. Mice were perfused intracardially with 4% sion of the S100B protein is in the brain and is found primarily NEUROBIOLOGY in the cytoplasm of astrocytes (9). Results of in vitro studies paraformaldehyde in 0.1M phosphate buffer (pH 7.4) at 4°C. suggest a variety of intracellular functions of S100B, including The brains were then removed and processed for paraffin cell growth, cell structure, energy metabolism, and calcium homeostasis (8). S100B is secreted from astrocytes, suggesting Abbreviations: LTP, long-term potentiation; fEPSP, field excitatory postsynaptic potentials; that it might also have extracellular functions. Exogenous S100B D-APV, D(Ϫ)-2-amino-5-phosphonopentanoic acid; NMDA, N-methyl-D-aspartate. increases intracellular calcium concentrations in both cultured §To whom reprint requests should be addressed. E-mail: [email protected]. neurons and astrocytes (10). Elevated neuronal calcium might The publication costs of this article were defrayed in part by page charge payment. This affect calcium-dependent processes involved in synaptic plastic- article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. ity, and the role of S100B in neuronal synaptic plasticity is a §1734 solely to indicate this fact. www.pnas.org͞cgi͞doi͞10.1073͞pnas.052020999 PNAS ͉ March 19, 2002 ͉ vol. 99 ͉ no. 6 ͉ 4037–4042 Downloaded by guest on September 27, 2021 embedding. Sagittal sections (4-␮m-thick) were used for hema- each of the four trials. The time taken to reach the platform toxylin-eosin staining and S100B immunohistochemical staining (escape latency) was recorded. A probe test was performed 3 h (anti-S100B monoclonal antibody, clone SH-B1, diluted 1:2500; after the last hidden platform trial. In the probe test, the Sigma). Immunoreactivity was visualized using a Vectastain platform was removed and each mouse was allowed to swim for ABC kit (Vector Laboratories). 60 s. The swimming path length, time spent in the quadrant that had contained the platform (trained quadrant), and number of Electrophysiological Analysis. Transverse hippocampal slices (400- times the mice crossed the area where the platform had been ␮m-thick) from adult mice (3–6 months old) were perfused in an located were recorded. Three days after the probe test, mice immersion-type recording chamber with artificial cerebrospinal were tested in a visible platform task for 3 consecutive days. In ͞ ͞ ͞ ͞ fluid (ACSF, in mM; 118 NaCl 3 KCl 2 CaCl2 1 MgCl2 1 this task, the platform was made visible by attaching a black cubic ͞ ͞ NaH2PO4 25 NaHCO3 10 glucose) at room temperature. Field landmark to the platform. In all of these experiments, movement excitatory postsynaptic potentials (fEPSPs) were recorded in the of each mouse was monitored with a CCD camera and processed CA1 stratum radiatum by using glass pipettes filled with ACSF. with NIH IMAGE WM 2.12 (O’hara & Co., Tokyo), a modified Test stimuli of 0.1-ms duration were delivered to the Schaffer version of the software based on the public domain NIH IMAGE collaterals at 0.05 Hz with a monopolar platinum electrode and program. fEPSPs were amplified using an Axopatch 200B amplifier (Axon Contextual fear conditioning test. A fear conditioning shock Instruments, Foster City, CA). The stimulus strength was ad- chamber (10 ϫ 10 ϫ 10 cm high) was used. Mice were put in the justed to produce a response of 40–50% of the maximum fEPSP chamber and conditioned by a single electrical foot shock (0.75 amplitude. fEPSP slope was calculated from the average of six mA, 2 s). The mice were allowed to stay in the chamber for responses evoked at 0.05 Hz and the magnitude of LTP was another 1 min for measurement of immediate freezing, and then defined as the relative change in the fEPSP slope compared with placed back into their home cage. After 24 h, the mice were again the averaged baseline response monitored for 14 min before the put in the same chamber and monitored for 5 min without tetanic stimulation. Stock solutions of drugs and recombinant electrical shock. Movement of each mouse was monitored using S100B were dissolved in ACSF and stored in reservoirs. Drugs a CCD camera and processed with NIH IMAGE FZ 2.17 (O’hara & were applied by switching reservoirs. The electrophysiological Co.), a modified version of the software based on the public experiments, except for D-APV [D(Ϫ)-2-amino-5-phosphono- domain NIH IMAGE program.
Load more

Recommended publications
  • Unnatural Verticilide Enantiomer Inhibits Type 2 Ryanodine Receptor-Mediated Calcium Leak and Is Antiarrhythmic
    Unnatural verticilide enantiomer inhibits type 2 ryanodine receptor-mediated calcium leak and is antiarrhythmic Suzanne M. Batistea,1, Daniel J. Blackwellb,1, Kyungsoo Kimb,1, Dmytro O. Kryshtalb, Nieves Gomez-Hurtadob, Robyn T. Rebbeckc, Razvan L. Corneac, Jeffrey N. Johnstona,2, and Bjorn C. Knollmannb,2 aDepartment of Chemistry, Vanderbilt University, Nashville, TN 37235; bDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232; and cDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455 Edited by Dale L. Boger, The Scripps Research Institute, La Jolla, CA, and approved January 15, 2019 (received for review September 27, 2018) Ca2+ leak via ryanodine receptor type 2 (RyR2) can cause poten- heart diseases associated with both atrial and ventricular arrhyth- tially fatal arrhythmias in a variety of heart diseases and has also mia (9). Mutations in RyR2 and its binding partners, which increase + been implicated in neurodegenerative and seizure disorders, mak- SR Ca2 leak, cause primary atrial and ventricular arrhythmia ing RyR2 an attractive therapeutic target for drug development. syndromes such as catecholaminergic polymorphic ventricular Here we synthesized and investigated the fungal natural product tachycardia (CPVT), providing strong evidence for the mechanistic and known insect RyR antagonist (−)-verticilide and several conge- contribution of RyR2 to arrhythmia risk in humans (10). Further ners to determine their activity against mammalian RyR2. Although support comes from gene-targeted mouse models of CPVT, where + the cyclooligomeric depsipeptide natural product (−)-verticilide had catecholamine-induced spontaneous Ca2 release from the SR no effect, its nonnatural enantiomer [ent-(+)-verticilide] signifi- via RyR2 generates potentially fatal cardiac arrhythmias (11, 12).
    [Show full text]
  • S100B Promotes Glioma Growth Through Chemoattraction of Myeloid-Derived Macrophages
    Published OnlineFirst May 29, 2013; DOI: 10.1158/1078-0432.CCR-12-3725 Clinical Cancer Human Cancer Biology Research S100B Promotes Glioma Growth through Chemoattraction of Myeloid-Derived Macrophages Huaqing Wang1, Leying Zhang5, Ian Y. Zhang5, Xuebo Chen2, Anna Da Fonseca8, Shihua Wu3, Hui Ren2, Sam Badie5, Sam Sadeghi5, Mao Ouyang4, Charles D. Warden6, and Behnam Badie5,7 Abstract þ Purpose: S100B is member of a multigenic family of Ca2 -binding proteins, which is overexpressed by gliomas. Recently, we showed that low concentrations of S100B attenuated microglia activation through the induction of Stat3. We hypothesized that overexpression of S100B in gliomas could promote tumor growth by modulating the activity of tumor-associated macrophages (TAM). Experimental Design: We stably transfected GL261 glioma cell lines with constructs that overexpressed (S100Bhigh) or underexpressed (S100Blow) S100B and compared their growth characteristics to intracranial wild-type (S100Bwt) tumors. Results: Downregulation of S100B in gliomas had no impact on cell division in vitro but abrogated tumor growth in vivo. Interestingly, compared to S100Blow tumors, S100Bwt and S100Bhigh intracranial gliomas exhi- bited higher infiltration of TAMs, stronger inflammatory cytokine expression, and increased vascularity. To identify the potential mechanisms involved, the expression of the S100B receptor, receptor for advanced glycation end products (RAGE), was evaluated in gliomas. Although S100B expression induced RAGE in vivo, RAGE ablation in mice did not significantly inhibit TAM infiltration into gliomas, suggesting that other pathways were involved in this process. To evaluate other mechanisms responsible for TAM chemoattraction, we then examined chemokine pathways and found that C-C motif ligand 2 (CCL2) was upregulated in S100Bhigh tumors.
    [Show full text]
  • Association of Serum S100B, S100A1 and Zinc-Α2
    Progress in Nutrition 2019; Vol. 21, Supplement 1: 154-162 DOI: 10.23751/pn.v21i1-S.5846 © Mattioli 1885 Original articles Association of serum S100B, S100A1 and Zinc-α2- Glycoprotein levels with anthropometric, metabolic and clinical indices in men and women Sorayya Kheirouri1, Mohammad Alizadeh1, Elham Ebrahimi2, Masoumeh Jabbari2 1Associate Professor, Department of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran - Email: kheirouris@tbzmed. ac.ir, [email protected]; 2MSc. student, Department of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran Summary. Objectives: We aimed to investigate serum levels of S100B, S100A1, and Zinc-α2- glycoprotein (ZAG) in men and women and to find association of these proteins with anthropometric, metabolic and clini- cal indices. Methods: Eighty-eight apparently healthy adults, 43 men and 45 women, participated in the study. The participants’ body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP) were measured. Serum levels of total cholesterol (TC), triglyceride (TG), low and high den- sity lipoprotein cholesterol (LDL-C and HDL-C), fasting blood sugar (FBS), insulin, S100B, S100A1 and ZAG protein were examined by enzymatic and ELISA laboratory methods. Homeostatic model assessment- insulin resistance (HOMA-IR) index was calculated. Results: Serum levels of S100B, S100A1 and ZAG were comparable between men and women groups. S100B protein was positively associated with TG (r= 0.41, p= 0.006), SBP (r= 0.46, p= 0.002), and DBP (r= 0.37, p= 0.02), but negatively with HDL-c in men. Serum levels of S100A1 were significantly and negatively correlated with WC (r= -0.33, p= 0.03), TG (r= -0.37, p= 0.01), insulin (r= -0.31, p= 0.04) and HOMA-IR (r= -0.32, p= 0.03), in women.
    [Show full text]
  • Ahnaks Are a Class of Giant Propeller-Like Proteins That Associate with Calcium Channel Proteins of Cardiomyocytes and Other Cells
    The AHNAKs are a class of giant propeller-like proteins that associate with calcium channel proteins of cardiomyocytes and other cells Akihiko Komuro*, Yutaka Masuda*, Koichi Kobayashi, Roger Babbitt, Murat Gunel, Richard A. Flavell, and Vincent T. Marchesi† Departments of Pathology and Immunobiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510 Contributed by Vincent T. Marchesi, December 31, 2003 To explore the function of the giant AHNAK molecule, first de- mechanisms, one operating at the cell surface in collaboration with scribed in 1992 [Shtivelman, E., Cohen, F. E. & Bishop, J. M. (1992) calcium channels, and the second, PLC activation, which is a process Proc. Natl. Acad. Sci. USA 89, 5472–5476], we created AHNAK null that could potentially take place at multiple points throughout the mice by homologous recombination. Homozygous knockouts cell. showed no obvious phenotype, but revealed instead a second The arrangement of channel proteins at the cell surface is AHNAK-like molecule, provisionally designated AHNAK2. Like the believed to be controlled by multidomain polypeptides known as original AHNAK, AHNAK2 is a 600-kDa protein composed of a large scaffolding proteins that link together activated channels at specific number of highly conserved repeat segments. Structural predic- points on the membrane surface. Scaffolding proteins also coordi- tions suggest that the repeat segments of both AHNAKs may have nate the activities of multienzyme complexes by physically linking as their basic framework a series of linked, antiparallel ␤-strands them together, and as in the case with AHNAK, they are often similar to those found in ␤-propeller proteins.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Rage (Receptor for Advanced Glycation End Products) in Melanoma
    RAGE (RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS) IN MELANOMA PROGRESSION A Dissertation Submitted to the Graduate Faculty of the North Dakota State University of Agriculture and Applied Science By Varsha Meghnani In Partial Fulfillment for the Degree of DOCTOR OF PHILOSOPHY Major Department: Pharmaceutical Sciences May 2014 Fargo, North Dakota North Dakota State University Graduate School Title RAGE (RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS) IN MELANOMA PROGRESSION By VARSHA MEGHNANI The Supervisory Committee certifies that this disquisition complies with North Dakota State University’s regulations and meets the accepted standards for the degree of DOCTOR OF PHILOSOPHY SUPERVISORY COMMITTEE: ESTELLE LECLERC Chair BIN GUO STEPHEN O’ROURKE JANE SCHUH Approved: 5/22/2014 JAGDISH SINGH Date Department Chair ABSTRACT The Receptor for Advanced Glycation End Products (RAGE) and its ligands are expressed in multiple cancer types and are implicated in cancer progression. Our lab has previously reported higher transcript levels of RAGE and S100B in advanced staged melanoma patients. The contribution of RAGE in the pathophysiology of melanoma has not been well studied. Based on previous reports, we hypothesized that RAGE, when over-expressed in melanoma cells, promotes melanoma progression. To study the pathogenic role of RAGE in melanoma, a primary melanoma cell line, WM115, was selected and stably transfected with full length RAGE (FL_RAGE) to generate a model cell line over-expressing RAGE (WM115_RAGE). WM266, a sister cell line of WM115, originated from a metastatic tumor of the same patient was used as a metastatic control cell line in the study. After assessing the expression levels of RAGE in the transfected cells, the influence of RAGE on their cellular properties was examined.
    [Show full text]
  • The Impact of High Glucose Or Insulin Exposure on S100B Protein Levels, Oxidative and Nitrosative Stress and DNA Damage in Neuron-Like Cells
    International Journal of Molecular Sciences Article The Impact of High Glucose or Insulin Exposure on S100B Protein Levels, Oxidative and Nitrosative Stress and DNA Damage in Neuron-Like Cells Adriana Kubis-Kubiak 1,* , Benita Wiatrak 2 and Agnieszka Piwowar 1 1 Department of Toxicology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland; [email protected] 2 Department of Pharmacology, Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 2, 50-345 Wroclaw, Poland; [email protected] * Correspondence: [email protected] Abstract: Alzheimer’s disease (AD) is attracting considerable interest due to its increasing number of cases as a consequence of the aging of the global population. The mainstream concept of AD neuropathology based on pathological changes of amyloid b metabolism and the formation of neurofibrillary tangles is under criticism due to the failure of Ab-targeting drug trials. Recent findings have shown that AD is a highly complex disease involving a broad range of clinical manifestations as well as cellular and biochemical disturbances. The past decade has seen a renewed importance of metabolic disturbances in disease-relevant early pathology with challenging areas in establishing the role of local micro-fluctuations in glucose concentrations and the impact of insulin on neuronal function. The role of the S100 protein family in this interplay remains unclear and is the aim of this research. Intracellularly the S100B protein has a protective effect on neurons against the toxic effects Citation: Kubis-Kubiak, A.; Wiatrak, of glutamate and stimulates neurites outgrowth and neuronal survival. At high concentrations, B.; Piwowar, A.
    [Show full text]
  • Structural Basis for S100B Interaction with Its Target Proteins
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author J Mol Genet Manuscript Author Med. Author Manuscript Author manuscript; available in PMC 2019 March 07. Published in final edited form as: J Mol Genet Med. 2018 ; 12(3): . doi:10.4172/1747-0862.1000366. Structural Basis for S100B Interaction with its Target Proteins KD Prez and L Fan* Department of Biochemistry, University of California Riverside, 900 University Ave, Riverside, California, USA Abstract The S100B protein is an intra- and extracellular signaling protein that plays a role in a multitude of cellular processes and abnormal S100B is associated with various neurological diseases and cancers. S100B recognizes and binds effector proteins in a calcium-dependent manner. S100B has been shown to interact with the actin capping protein CapZ, protein kinase C, Hdm2 and 4, RAGE receptor, and p53, among others. These protein partners interact with a common area on the S100B protein surface, validating the method of using the consensus sequence for S100B target search. In addition, each S100B target protein distinguishes itself by additional contacts with S100B. This perspective suggests that the combination of sequence homology search and structural analysis promises to identify newer S100B-binding partners beyond the use of the consensus sequence alone as the given example in the XPB subunit of the TFIIH general transcription factor. XPB is a helicase required for both transcription and DNA repair. Inherited xpb mutations are associated with human disease Xeroderma Pigmentasum, Cockayne syndrome, and trichothiodystrophy. S100B protein is likely associated with much more biological pathways and processes. We believe that S100B will attract more and more attentions in the scientific community and S100B related studies will have important implications in human health and medicine.
    [Show full text]
  • 8296.Full.Pdf
    Inflammation-Induced Chondrocyte Hypertrophy Is Driven by Receptor for Advanced Glycation End Products This information is current as Denise L. Cecil, Kristen Johnson, John Rediske, Martin of September 28, 2021. Lotz, Ann Marie Schmidt and Robert Terkeltaub J Immunol 2005; 175:8296-8302; ; doi: 10.4049/jimmunol.175.12.8296 http://www.jimmunol.org/content/175/12/8296 Downloaded from References This article cites 43 articles, 13 of which you can access for free at: http://www.jimmunol.org/content/175/12/8296.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 28, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Inflammation-Induced Chondrocyte Hypertrophy Is Driven by Receptor for Advanced Glycation End Products1 Denise L. Cecil,* Kristen Johnson,* John Rediske,‡ Martin Lotz,§ Ann Marie Schmidt,† and Robert Terkeltaub2* The multiligand receptor for advanced glycation end products (RAGE) mediates certain chronic vascular and neurologic degen- erative diseases accompanied by low-grade inflammation.
    [Show full text]
  • Current Projects and Publications
    Current projects and Publications Parminder J.S. Vig, PhD Professor of Neurology and Biochemistry Associate Professor of Neurobiology and Anatomical Sciences Funded Projects: National Institutes of Health (NINDS): RO3 Targeted Delivery of S100B inhibitory peptides to SCA1 Mouse Cerebellum. (MPI) Principal Investigator, March 2010-April 2013 Currier Spinocerebellar Research Fund Do glial proteins modulate ataxin- 1phosphorylation. Principal Investigator, Jan 2010-open Cure Ataxia.org: Ataxia: Ataxia Research at UMMC. Principal Investigator, Dec. 2010 –open Balance Disorders Inc: Dopamine D2 Receptor Agonist Bromocriptine as a Potential Therapeutic for SCA1.Principal Investigator, 07/01/2011 – 06/30/2012 Pending/under preparation: Intramural Research Support Program, UMMC.Targeting therapeutics to cerebellum using heat sensitive polypeptide carriers. Principal Investigator The Micheal J. Fox Foundation Title: Validation of ASIC1a as a Therapeutic Target for Parkinson's Disease Principal Investigators: Bidwell and Vig National Institutes of Health (NINDS): R21, Targeting cerebellum with thermally sensitive therapeutic peptides. (MPI) Principal Investigator: Vig and Raucher National Institutes of Health (NINDS): R01, Dopamine against as therapeutics for SCA1.Principal Investigator: Vig Previous: National Ataxia Foundation: Cytokines in Human Neurodegenerative Disorders. Principal Investigator 1993-1994 ($2,045) National Ataxia Foundation: In vivo effects of insulin-like growth factor-I on cerebellar degeneration in lurcher mouse. Principal Investigator 1994-1995 ($5,000). Pediatrics Research Support Grant: Glial cell responses in the spinal cord during motor neuron degeneration produced by B-iminodipropiononitrile in rats. Co-Investigator 1994- 1995 ($ 10,000). UMC Seed Money: Role of Calcium Binding proteins in hippocampal degeneration in developing mice following intrauterine exposure to domoic acid. Principal Investigator 1994-1997 ($5,000) National Ataxia Foundation: Calcium binding proteins in patients with spinocerebellar ataxias.
    [Show full text]
  • Oxidative Stress-Induced S100B Accumulation Converts Myoblasts Into Brown Adipocytes Via an NF-Κb/YY1/Mir-133 Axis and NF-Κb/YY1/BMP-7 Axis
    Cell Death and Differentiation (2017) 24, 2077–2088 & 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 1350-9047/17 www.nature.com/cdd Oxidative stress-induced S100B accumulation converts myoblasts into brown adipocytes via an NF-κB/YY1/miR-133 axis and NF-κB/YY1/BMP-7 axis Giulio Morozzi1,4, Sara Beccafico1,2,4, Roberta Bianchi1, Francesca Riuzzi1,2, Ilaria Bellezza1, Ileana Giambanco1, Cataldo Arcuri1, Alba Minelli1 and Rosario Donato*,1,2,3 Muscles of sarcopenic people show hypotrophic myofibers and infiltration with adipose and, at later stages, fibrotic tissue. The origin of infiltrating adipocytes resides in fibro-adipogenic precursors and nonmyogenic mesenchymal progenitor cells, and in satellite cells, the adult stem cells of skeletal muscles. Myoblasts and brown adipocytes share a common Myf5+ progenitor cell: the cell fate depends on levels of bone morphogenetic protein 7 (BMP-7), a TGF-β family member. S100B, a Ca2+-binding protein of the EF-hand type, is expressed at relatively high levels in myoblasts from sarcopenic humans and exerts anti-myogenic effects via NF-κB-dependent inhibition of MyoD, a myogenic transcription factor acting upstream of the essential myogenic factor, myogenin. Adipogenesis requires high levels of ROS, and myoblasts of sarcopenic subjects show elevated ROS levels. Here we show that: (1) ROS overproduction in myoblasts results in upregulation of S100B levels via NF-κB activation; and (2) ROS/NF-κB-induced accumulation of S100B causes myoblast transition into brown adipocytes. S100B activates an NF-κB/Ying Yang 1 axis that negatively regulates the promyogenic and anti-adipogenic miR-133 with resultant accumulation of the brown adipogenic transcription regulator, PRDM-16.
    [Show full text]
  • Increased S100B Blood Levels in Unmedicated and Treated
    Molecular Psychiatry (2001) 6, 445–449 2001 Nature Publishing Group All rights reserved 1359-4184/01 $15.00 www.nature.com/mp ORIGINAL RESEARCH ARTICLE Increased S100B blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology M Rothermundt1, U Missler2, V Arolt1, M Peters1, J Leadbeater3, M Wiesmann2, S Rudolf4, KP Wandinger5 and H Kirchner4 1Department of Psychiatry, University of Muenster School of Medicine, Albert-Schweitzer-Str 11, D-48129 Muenster, Germany; 2Department of Neuroradiology, Medical University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany; 3Psychiatric Hospital, Friedrich-Ebert-Str, D-23774 Heiligenhafen, Germany; 4Institute of Immunology and Transfusion Medicine, Medical University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany; 5Department of Neurology, Charite Campus Mitte, NWFZ 2680, R 04 023, Schumannstr 20/21, D-10117 Berlin, Germany Keywords: nerve tissue protein S100; schizophrenia; anti- The term S100 comprises a heterogeneous family of psychotic agents; negative symptomatology; psychiatric acidic calcium-binding proteins of which the two pro- status teins S100A1 and S100B are considered to be the most S100B, a calcium-binding protein produced by astroglial relevant members regarding neurological disease.3 cells, is a marker of astroglial cellular integrity. It has S100B predominates in the brain. S100A1 and S100B been shown to be increased in acute brain damage and form dimeric proteins with a molecular weight of 21 neurodegeneration. A recent study showed increased kDA, which have previously been named S100a S100B levels in medicated acutely psychotic patients (S100A1–S100B), S100b (S100B–S100B), and S100a0 with schizophrenia. The study presented here included (S100A–S100A).4 S100B is synthesized mainly by 26 drug-free patients with acute schizophrenia and 26 astrocytes and evolves paracrine and autocrine effects matched healthy controls.
    [Show full text]