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Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability

2021-11-30Journal article Open access
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dc.contributor.authorBerrocal, Maria
dc.contributor.authorCordoba-Granados, Juan J.
dc.contributor.authorCarabineiro, Sónia A. C.
dc.contributor.authorGutierrez-Merino, Carlos
dc.contributor.authorAureliano, Manuel
dc.contributor.authorMata, Ana M.
dc.date.accessioned2022-01-10T14:58:05Z
dc.date.available2022-01-10T14:58:05Z
dc.date.issued2021-11-30
dc.date.updated2021-12-23T15:06:53Z
dc.description.abstractPlasma membrane calcium ATPases (PMCA) are key proteins in the maintenance of calcium (Ca<sup>2+</sup>) homeostasis. Dysregulation of PMCA function is associated with several human pathologies, including neurodegenerative diseases, and, therefore, these proteins are potential drug targets to counteract those diseases. Gold compounds, namely of Au(I), are well-known for their therapeutic use in rheumatoid arthritis and other diseases for centuries. Herein, we report the ability of dichloro(2-pyridinecarboxylate)gold(III) (<b>1</b>), chlorotrimethylphosphinegold(I) (<b>2</b>), 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidenegold(I) chloride (<b>3</b>), and chlorotriphenylphosphinegold(I) (<b>4</b>) compounds to interfere with the Ca<sup>2+</sup>-ATPase activity of pig brain purified PMCA and with membranes from SH-SY5Y neuroblastoma cell cultures. The Au(III) compound (<b>1</b>) inhibits PMCA activity with the IC<sub>50</sub> value of 4.9 µM, while Au(I) compounds (<b>2</b>, <b>3</b>, and <b>4</b>) inhibit the protein activity with IC<sub>50</sub> values of 2.8, 21, and 0.9 µM, respectively. Regarding the native substrate MgATP, gold compounds <b>1</b> and <b>4</b> showed a non-competitive type of inhibition, whereas compounds <b>2</b> and <b>3</b> showed a mixed type of inhibition. All gold complexes showed cytotoxic effects on human neuroblastoma SH-SY5Y cells, although compounds <b>1</b> and <b>3</b> were more cytotoxic than compounds <b>2</b> and <b>4</b>. In summary, this work shows that both Au (I and III) compounds are high-affinity inhibitors of the Ca<sup>2+</sup>-ATPase activity in purified PMCA fractions and in membranes from SH-SY5Y human neuroblastoma cells. Additionally, they exert strong cytotoxic effects.pt_PT
dc.description.sponsorshipProjects BFU2017-85723-P (to A.M.M. and C.G.-M.), and PID2020-115512GB-I00 (to A.M.M.) funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”. We acknowledge Fundação para a Ciência e a Tecnologia (FCT) project UIDB/04326/2020, Associate Laboratory for Green Chemistry–LAQV, financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020) and Scientific Employment Stimulus-Institutional Call (CEECINST/00102/2018).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMetals 11 (12): 1934 (2021)pt_PT
dc.identifier.doi10.3390/met11121934pt_PT
dc.identifier.issn2075-4701
dc.identifier.urihttp://hdl.handle.net/10400.1/17459
dc.language.isoengpt_PT
dc.publisherMDPIpt_PT
dc.relationAlgarve Centre for Marine Sciences
dc.relationAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
dc.relationAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
dc.relationNot Available
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectGold compoundspt_PT
dc.subjectPMCApt_PT
dc.subjectCa2+-ATPasept_PT
dc.subjectCalcium homeostasispt_PT
dc.subjectSH-SY5Y human neuroblastoma cellspt_PT
dc.titleGold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viabilitypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
oaire.awardTitleAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
oaire.awardTitleNot Available
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04326%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50006%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC INST 2018/CEECINST%2F00102%2F2018%2FCP1567%2FCT0001/PT
oaire.citation.issue12pt_PT
oaire.citation.startPage1934pt_PT
oaire.citation.titleMetalspt_PT
oaire.citation.volume11pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamCEEC INST 2018
person.familyNameAureliano
person.givenNameManuel
person.identifier584146
person.identifier.ciencia-idAA14-3490-DC5E
person.identifier.orcid0000-0003-4858-3201
person.identifier.ridI-3283-2012
person.identifier.scopus-author-id6603412860
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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