A Potent Tartrate Resistant Acid Phosphatase Inhibitor to Study the Function of TRAP in Alveolar Macrophages

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorBOORSMA, Carian E.
dc.contributor.authorVEEN, T. Anienke van der
dc.contributor.authorPUTRI, Kurnia S. S.
dc.contributor.authorALMEIDA, Andreia de
dc.contributor.authorDRAIJER, Christina
dc.contributor.authorMAUAD, Thais
dc.contributor.authorFEJER, Gyorgy
dc.contributor.authorBRANDSMA, Corry-Anke
dc.contributor.authorBERGE, Maarten van den
dc.contributor.authorBOSSE, Yohan
dc.contributor.authorSIN, Don
dc.contributor.authorHAO, Ke
dc.contributor.authorREITHMEIER, Anja
dc.contributor.authorANDERSSON, Goran
dc.contributor.authorOLINGA, Peter
dc.contributor.authorTIMENS, Wim
dc.contributor.authorCASINI, Angela
dc.contributor.authorMELGERT, Barbro N.
dc.date.accessioned2017-12-12T13:19:59Z
dc.date.available2017-12-12T13:19:59Z
dc.date.issued2017
dc.description.abstractThe enzyme tartrate resistant acid phosphatase (TRAP, two isoforms 5a and 5b) is highly expressed in alveolar macrophages, but its function there is unclear and potent selective inhibitors of TRAP are required to assess functional aspects of the protein. We found higher TRAP activity/expression in lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma compared to controls and more TRAP activity in lungs of mice with experimental COPD or asthma. Stimuli related to asthma and/or COPD were tested for their capacity to induce TRAP. Receptor activator of NF-kappa b ligand (RANKL) and Xanthine/Xanthine Oxidase induced TRAP mRNA expression in mouse macrophages, but only RANKL also induced TRAP activity in mouse lung slices. Several Au(III) coordination compounds were tested for their ability to inhibit TRAP activity and [Au(4,4'-dimethoxy-2,2'-bipyridine)Cl-2][PF6] (AubipyOMe) was found to be the most potent inhibitor of TRAP5a and 5b activity reported to date (IC50 1.3 and 1.8 mu M respectively). AubipyOMe also inhibited TRAP activity in murine macrophage and human lung tissue extracts. In a functional assay with physiological TRAP substrate osteopontin, AubipyOMe inhibited mouse macrophage migration over osteopontin-coated membranes. In conclusion, higher TRAP expression/activity are associated with COPD and asthma and TRAP is involved in regulating macrophage migration.
dc.description.indexMEDLINE
dc.description.sponsorshipDutch Lung Fund [4.1.15.002]
dc.description.sponsorshipCOST action [BM1201]
dc.description.sponsorshipCNPq (Brazilian National Research Council)
dc.description.sponsorshipSwedish Research Council [K2015-99X-10363-23]
dc.identifier.citationSCIENTIFIC REPORTS, v.7, article ID 12570, 14p, 2017
dc.identifier.doi10.1038/s41598-017-12623-w
dc.identifier.issn2045-2322
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/24363
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.relation.ispartofScientific Reports
dc.rightsopenAccess
dc.rights.holderCopyright NATURE PUBLISHING GROUP
dc.subject.othergold organometallic compounds
dc.subject.otherros-generating activity
dc.subject.otherdendritic cells
dc.subject.othercopd patients
dc.subject.otherin-vitro
dc.subject.othergold(iii) compounds
dc.subject.othertissue macrophages
dc.subject.otherpulmonary-disease
dc.subject.otheranticancer agents
dc.subject.othergene-expression
dc.subject.wosMultidisciplinary Sciences
dc.titleA Potent Tartrate Resistant Acid Phosphatase Inhibitor to Study the Function of TRAP in Alveolar Macrophages
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryInglaterra
hcfmusp.affiliation.countrySuécia
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryCanadá
hcfmusp.affiliation.countryPaís de Gales
hcfmusp.affiliation.countryHolanda
hcfmusp.affiliation.countryisonl
hcfmusp.affiliation.countryisogb
hcfmusp.affiliation.countryisoca
hcfmusp.affiliation.countryisous
hcfmusp.affiliation.countryisose
hcfmusp.author.externalBOORSMA, Carian E.:Univ Groningen, Groningen Res Inst Pharm, Dept Pharmacokinet Toxicol & Targeting, Groningen, Netherlands; Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands
hcfmusp.author.externalVEEN, T. Anienke van der:Univ Groningen, Groningen Res Inst Pharm, Dept Pharmacokinet Toxicol & Targeting, Groningen, Netherlands; Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands
hcfmusp.author.externalPUTRI, Kurnia S. S.:Univ Groningen, Groningen Res Inst Pharm, Dept Pharmaceut Technol & Biopharm, Groningen, Netherlands
hcfmusp.author.externalALMEIDA, Andreia de:Cardiff Univ, Sch Chem, Cardiff, S Glam, Wales
hcfmusp.author.externalDRAIJER, Christina:Univ Groningen, Groningen Res Inst Pharm, Dept Pharmacokinet Toxicol & Targeting, Groningen, Netherlands; Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands
hcfmusp.author.externalFEJER, Gyorgy:Univ Plymouth, Sch Biomed & Healthcare Sci, Peninsula Sch Med, Plymouth, Devon, England; Univ Plymouth, Sch Biomed & Healthcare Sci, Peninsula Sch Dent, Plymouth, Devon, England
hcfmusp.author.externalBRANDSMA, Corry-Anke:Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, Groningen, Netherlands; Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands
hcfmusp.author.externalBERGE, Maarten van den:Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, Groningen, Netherlands; Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands
hcfmusp.author.externalBOSSE, Yohan:Laval Univ, Inst Univ Cardiol & Pneumol Quebec, Dept Mol Med, Quebec City, PQ, Canada
hcfmusp.author.externalSIN, Don:Univ British Columbia, Providence Heart Lung Inst, St Pauls Hosp, James Hogg Res Ctr, Vancouver, BC, Canada; Univ British Columbia, Resp Div, Dept Med Vancouver, Vancouver, BC, Canada
hcfmusp.author.externalHAO, Ke:Merck Res Labs, Boston, MA USA
hcfmusp.author.externalREITHMEIER, Anja:Karolinska Univ Hosp, Karolinska Inst, Div Pathol, Dept Lab Med LABMED, H5,F46, Huddinge, Sweden
hcfmusp.author.externalANDERSSON, Goran:Karolinska Univ Hosp, Karolinska Inst, Div Pathol, Dept Lab Med LABMED, H5,F46, Huddinge, Sweden
hcfmusp.author.externalOLINGA, Peter:Univ Groningen, Groningen Res Inst Pharm, Dept Pharmaceut Technol & Biopharm, Groningen, Netherlands
hcfmusp.author.externalTIMENS, Wim:Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, Groningen, Netherlands; Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands
hcfmusp.author.externalCASINI, Angela:Univ Groningen, Groningen Res Inst Pharm, Dept Pharmacokinet Toxicol & Targeting, Groningen, Netherlands; Cardiff Univ, Sch Chem, Cardiff, S Glam, Wales
hcfmusp.author.externalMELGERT, Barbro N.:Univ Groningen, Groningen Res Inst Pharm, Dept Pharmacokinet Toxicol & Targeting, Groningen, Netherlands; Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands
hcfmusp.citation.scopus14
hcfmusp.contributor.author-fmusphcTHAIS MAUAD
hcfmusp.description.articlenumber12570
hcfmusp.description.volume7
hcfmusp.origemWOS
hcfmusp.origem.pubmed28974738
hcfmusp.origem.scopus2-s2.0-85030554385
hcfmusp.origem.wosWOS:000412138800006
hcfmusp.publisher.cityLONDON
hcfmusp.publisher.countryENGLAND
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