A Potent Tartrate Resistant Acid Phosphatase Inhibitor to Study the Function of TRAP in Alveolar Macrophages
dc.contributor.author | Boorsma, CE | |
dc.contributor.author | van der Veen, TA | |
dc.contributor.author | Putri, KSS | |
dc.contributor.author | de Almeida, A | |
dc.contributor.author | Draijer, C | |
dc.contributor.author | Mauad, T | |
dc.contributor.author | Fejer, Gyorgy | |
dc.contributor.author | Brandsma, C-A | |
dc.contributor.author | van den Berge, M | |
dc.contributor.author | Bossé, Yohan | |
dc.contributor.author | Sin, D | |
dc.contributor.author | Hao, K | |
dc.contributor.author | Reithmeier, A | |
dc.contributor.author | Andersson, G | |
dc.contributor.author | Olinga, P | |
dc.contributor.author | Timens, Wim | |
dc.contributor.author | Casini, A | |
dc.contributor.author | Melgert, Barbro | |
dc.date.accessioned | 2017-11-27T13:14:27Z | |
dc.date.available | 2017-11-27T13:14:27Z | |
dc.date.issued | 2017-10-03 | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.other | 12570 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/10278 | |
dc.description.abstract |
<jats:title>Abstract</jats:title><jats:p>The 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-κb 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<jats:sub>2</jats:sub>][PF<jats:sub>6</jats:sub>] (AubipyOMe) was found to be the most potent inhibitor of TRAP5a and 5b activity reported to date (IC50 1.3 and 1.8 μM 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.</jats:p> | |
dc.format.extent | 12570- | |
dc.format.medium | Electronic | |
dc.language | en | |
dc.language.iso | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.subject | Animals | |
dc.subject | Asthma | |
dc.subject | Coordination Complexes | |
dc.subject | Enzyme Inhibitors | |
dc.subject | Gene Expression Regulation | |
dc.subject | Gold | |
dc.subject | Humans | |
dc.subject | Macrophages, Alveolar | |
dc.subject | Mice | |
dc.subject | Osteopontin | |
dc.subject | Pulmonary Disease, Chronic Obstructive | |
dc.subject | RANK Ligand | |
dc.subject | RNA, Messenger | |
dc.subject | Tartrate-Resistant Acid Phosphatase | |
dc.subject | Xanthine Oxidase | |
dc.title | A Potent Tartrate Resistant Acid Phosphatase Inhibitor to Study the Function of TRAP in Alveolar Macrophages | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000412138800006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 1 | |
plymouth.volume | 7 | |
plymouth.publication-status | Published online | |
plymouth.journal | Scientific Reports | |
dc.identifier.doi | 10.1038/s41598-017-12623-w | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/School of Biomedical Sciences | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/Research Groups | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED) | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
plymouth.organisational-group | /Plymouth/Users by role/Researchers in ResearchFish submission | |
dc.publisher.place | England | |
dcterms.dateAccepted | 2017-09-13 | |
dc.identifier.eissn | 2045-2322 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1038/s41598-017-12623-w | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2017-10-03 | |
rioxxterms.type | Journal Article/Review |