S100A4 Inhibits Cell Proliferation by Interfering with the RAGE V Domain-S100A1
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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). -
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. -
Cellular Responses to Erbb-2 Overexpression in Human Mammary Luminal Epithelial Cells: Comparison of Mrna and Protein Expression
British Journal of Cancer (2004) 90, 173 – 181 & 2004 Cancer Research UK All rights reserved 0007 – 0920/04 $25.00 www.bjcancer.com Cellular responses to ErbB-2 overexpression in human mammary luminal epithelial cells: comparison of mRNA and protein expression SL White1, S Gharbi1, MF Bertani1, H-L Chan1, MD Waterfield1 and JF Timms*,1 1 Ludwig Institute for Cancer Research, Wing 1.1, Cruciform Building, Gower Street, London WCIE 6BT, UK Microarray analysis offers a powerful tool for studying the mechanisms of cellular transformation, although the correlation between mRNA and protein expression is largely unknown. In this study, a microarray analysis was performed to compare transcription in response to overexpression of the ErbB-2 receptor tyrosine kinase in a model mammary luminal epithelial cell system, and in response to the ErbB-specific growth factor heregulin b1. We sought to validate mRNA changes by monitoring changes at the protein level using a parallel proteomics strategy, and report a surprisingly high correlation between transcription and translation for the subset of genes studied. We further characterised the identified targets and relate differential expression to changes in the biological properties of ErbB-2-overexpressing cells. We found differential regulation of several key cell cycle modulators, including cyclin D2, and downregulation of a large number of interferon-inducible genes, consistent with increased proliferation of the ErbB-2- overexpressing cells. Furthermore, differential expression of genes involved in extracellular matrix modelling and cellular adhesion was linked to altered adhesion of these cells. Finally, we provide evidence for enhanced autocrine activation of MAPK signalling and the AP-1 transcription complex. -
S100 Calcium-Binding Protein S100 Proteins
S S100 Calcium-Binding Protein experiments showed the S100 protein fraction consti- tuted two different dimeric species comprised of two ▶ S100 Proteins b protomers (S100B) or an a, b heterodimer (Isobe et al. 1977). Early members of the S100 protein family were frequently given suffixes based on their localiza- tion or molecular size and included S100P (placental), S100 Proteins S100C (cardiac or calgizzarin), p11 (11 kDa), and MRP8/MRP14 (myeloid regulatory proteins, 8 and Brian R. Dempsey, Anne C. Rintala-Dempsey and 14 kDa). In 1993, initial genetic studies showed that Gary S. Shaw six of the S100 genes were clustered on chromosome Department of Biochemistry, The University of 1q21 (Engelkamp et al. 1993), a number that has Western Ontario, London, ON, Canada expanded since. Based on this observation most of the proteins were renamed according to the physical order they occupy on the chromosome. These include Synonyms S100A1 (formerly S100a), S100A2 (formerly S100L), S100A10 (p11), S100A8/S100A14 (MRP8/MRP14). S100 calcium-binding protein A few S100 proteins are found on other chromosomes including S100B (21q21). Currently there are 27 known S100 family members: S100A1-A18, S100B, S100 Protein Family Members S100G, S100P, S100Z, trichohylin, filaggrin, filaggrin- 2, cornulin, and repetin (Table 1). S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, S100A7, S100A8, S100A9, S100A10, S100A11, S100A12, S100A13, S100A14, S100A15, S100A16, Role of S100 Proteins in Calcium Signaling S100B, S100P, S100G, S100Z, trichohylin, filaggrin, filaggrin-2, -
Human S100A4 (P9ka) Induces the Metastatic Phenotype Upon Benign Tumour Cells
Oncogene (1998) 17, 465 ± 473 1998 Stockton Press All rights reserved 0950 ± 9232/98 $12.00 http://www.stockton-press.co.uk/onc Human S100A4 (p9Ka) induces the metastatic phenotype upon benign tumour cells Bryony H Lloyd, Angela Platt-Higgins, Philip S Rudland and Roger Barraclough School of Biological Sciences, University of Liverpool, PO Box 147, Liverpool, L69 7ZB, UK The rodent S100-related calcium-binding protein, strengthened by the observation that transgenic mice, S100A4 induces metastasis in non-metastatic rat and expressing elevated levels of S100A4 (p9Ka) from 17 mouse benign mammary cells and co-operates with additional, position-independent rat S100A4 trans- benign-tumour-inducing changes in two transgenic mouse genes, fail to show any detectable phenotype (Davies, models, to yield metastatic mammary tumours. Co- 1993). When these mice are mated with transgenic mice transfection of the human gene for S100A4 with containing additional copies of the activated rodent c- pSV2neo into the benign rat mammary cell line, Rama erbB-2 oncogene, neu, under the control of the MMTV 37, yielded cells which expressed a low level of the LTR (Bouchard et al., 1989), ospring inheriting the endogenous S100A4 mRNA, and either high or neu oncogene suer sporadic mammary tumours after undetectable levels of human S100A4 mRNA. The cells 12 ± 14 months of repeated mating. In contrast which expressed a high level of human S100A4 mRNA ospring inheriting both neu and S100A4 transgenes induced metastasis in the benign rat mammary cell line show an elevated incidence of primary tumours, and, in Rama 37 in an in vivo assay, whereas the cells which addition, metastases in the lungs which account for up expressed an undetectable level of human S100A4 did to 24% of the total lung area (Davies et al., 1996). -
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. -
S100P Interacts with P53 While Pentamidine Inhibits This Interaction
biomolecules Article S100P Interacts with p53 while Pentamidine Inhibits This Interaction Revansiddha H. Katte 1 , Deepu Dowarha 1 , Ruey-Hwang Chou 2,3 and Chin Yu 1,* 1 Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan; [email protected] (R.H.K.); [email protected] (D.D.) 2 Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung 40402, Taiwan; [email protected] 3 Department of Biotechnology, Asia University, Taichung 41354, Taiwan * Correspondence: [email protected]; Tel.: +886-963-780-784; Fax: +886-35-711082 Abstract: S100P, a small calcium-binding protein, associates with the p53 protein with micromolar affinity. It has been hypothesized that the oncogenic function of S100P may involve binding-induced inactivation of p53. We used 1H-15N HSQC experiments and molecular modeling to study the molecular interactions between S100P and p53 in the presence and absence of pentamidine. Our experimental analysis indicates that the S100P-53 complex formation is successfully disrupted by pentamidine, since S100P shares the same binding site for p53 and pentamidine. In addition, we showed that pentamidine treatment of ZR-75-1 breast cancer cells resulted in reduced proliferation and increased p53 and p21 protein levels, indicating that pentamidine is an effective antagonist that interferes with the S100P-p53 interaction, leading to re-activation of the p53-21 pathway and inhibition of cancer cell proliferation. Collectively, our findings suggest that blocking the association between S100P and p53 by pentamidine will prevent cancer progression and, therefore, provide a new avenue for cancer therapy by targeting the S100P-p53 interaction. -
Differential Gene Expression in Colon Cancer of the Caecum Versus
374 COLON CANCER Gut: first published as 10.1136/gut.2003.036848 on 11 February 2005. Downloaded from Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid K Birkenkamp-Demtroder, S H Olesen, F B Sørensen, S Laurberg, P Laiho, L A Aaltonen, T F Ørntoft ............................................................................................................................... Gut 2005;54:374–384. doi: 10.1136/gut.2003.036848 Background and aims: There are epidemiological, morphological, and molecular differences between normal mucosa as well as between adenocarcinomas of the right and left side of the large bowel. The aim of this study was to investigate differences in gene expression. Methods: Oligonucleotide microarrays (GeneChip) were used to compare gene expression in 45 single See end of article for samples from normal mucosa and sporadic colorectal carcinomas (Dukes’ B and C) of the caecum authors’ affiliations compared with the sigmoid and rectosigmoid. Findings were validated by real time polymerase chain ....................... reaction. Correspondence to: Results: Fifty eight genes were found to be differentially expressed between the normal mucosa of the Professor T F Ørntoft, caecum and the sigmoid and rectosigmoid (p,0.01), including pS2, S100P, and a sialyltransferase, all Molecular Diagnostic being expressed at higher levels in the caecum. A total of 118 and 186 genes were differentially expressed Laboratory, Department of Clinical Biochemistry, between normal and right or left sided tumours of the colon, showing more pronounced differences in Aarhus University Dukes’ C than B tumours. Thirty genes differentially expressed in tumour tissue were common to Hospital/Skejby, adenocarcinomas of both sides, including known tumour markers such as the matrix metalloproteinases. -
Absence of S100A4 in the Mouse Lens Induces an Aberrant Retina-Specific Differentiation Program and Cataract
www.nature.com/scientificreports OPEN Absence of S100A4 in the mouse lens induces an aberrant retina‑specifc diferentiation program and cataract Rupalatha Maddala1*, Junyuan Gao2, Richard T. Mathias2, Tylor R. Lewis1, Vadim Y. Arshavsky1,3, Adriana Levine4, Jonathan M. Backer4,5, Anne R. Bresnick4 & Ponugoti V. Rao1,3* S100A4, a member of the S100 family of multifunctional calcium‑binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in diferentiating fber cells of the ocular lens and that S100A4 (−/−) knockout mice develop late‑onset cortical cataracts. Transcriptome profling of lenses from S100A4 (−/−) mice revealed a robust increase in the expression of multiple photoreceptor‑ and Müller glia‑specifc genes, as well as the olfactory sensory neuron‑specifc gene, S100A5. This aberrant transcriptional profle is characterized by corresponding increases in the levels of proteins encoded by the aberrantly upregulated genes. Ingenuity pathway network and curated pathway analyses of diferentially expressed genes in S100A4 (−/−) lenses identifed Crx and Nrl transcription factors as the most signifcant upstream regulators, and revealed that many of the upregulated genes possess promoters containing a high‑density of CpG islands bearing trimethylation marks at histone H3K27 and/or H3K4, respectively. In support of this fnding, we further documented that S100A4 (−/−) knockout lenses have altered levels of trimethylated H3K27 and H3K4. Taken together, -
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 -
S100A4 Purified Maxpab Mouse Polyclonal Antibody (B03P)
S100A4 purified MaxPab mouse polyclonal antibody (B03P) Catalog # : H00006275-B03P 規格 : [ 50 ug ] List All Specification Application Image Product Mouse polyclonal antibody raised against a full-length human S100A4 Western Blot (Transfected lysate) Description: protein. Immunogen: S100A4 (NP_002952.1, 1 a.a. ~ 101 a.a) full-length human protein. Sequence: MACPLEKALDVMVSTFHKYSGKEGDKFKLNKSELKELLTRELPSFLGKR TDEAAFQKLMSNLDSNRDNEVDFQEYCVFLSCIAMMCNEFFEGFPDKQ PRKK enlarge Host: Mouse Reactivity: Human Quality Control Antibody reactive against mammalian transfected lysate. Testing: Storage Buffer: In 1x PBS, pH 7.4 Storage Store at -20°C or lower. Aliquot to avoid repeated freezing and thawing. Instruction: MSDS: Download Datasheet: Download Applications Western Blot (Transfected lysate) Western Blot analysis of S100A4 expression in transfected 293T cell line (H00006275-T05) by S100A4 MaxPab polyclonal antibody. Lane 1: S100A4 transfected lysate(11.70 KDa). Lane 2: Non-transfected lysate. Protocol Download Gene Information Entrez GeneID: 6275 Page 1 of 2 2016/5/21 GeneBank NM_002961.2 Accession#: Protein NP_002952.1 Accession#: Gene Name: S100A4 Gene Alias: 18A2,42A,CAPL,FSP1,MTS1,P9KA,PEL98 Gene S100 calcium binding protein A4 Description: Omim ID: 114210 Gene Ontology: Hyperlink Gene Summary: The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in motility, invasion, and tubulin polymerization. -
Inhibits the Migration of Prostate Cancer Through Reducing S100A4, S100A2, and S100P Expression
5429 Original Article Knockdown of ferritin heavy chain (FTH) inhibits the migration of prostate cancer through reducing S100A4, S100A2, and S100P expression Cuixiu Lu1, Huijun Zhao2, Chenshuo Luo3, Ting Lei4, Man Zhang5,6,7^ 1Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China; 2Clinical Laboratory Medicine, Capital Medical University, Beijing, China; 3Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China; 4Beijing Shijitan Hospital, Capital Medical University, Beijing, China; 5Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China; 6Beijing Shijitan Hospital, Capital Medical University, Beijing, China; 7Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China Contributions: (I) Conception and design: C Lu, C Luo; (II) Administrative support: M Zhang; (III) Provision of study materials or patients: C Lu, T Lei; (IV) Collection and assembly of data: C Lu, H Zhao; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Man Zhang. Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing 100038, China. Email: [email protected]. Background: Ferritin plays a key role in the development of prostate cancer (PCa). Our earlier studies showed that the knockdown of ferritin heavy chain (FTH) suppressed the migration and invasion of the prostate cancer cell line (PC3). However, the mechanisms behind FTH in the cell migration regulation of PCa have not been thoroughly investigated. Methods: Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics was used to analyze the protein expression in PC3 cells with FTH knockdown by small interfering RNAs and negative control cells.