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

Detalhes bibliográficos
Autor(a) principal: Berrocal, Maria
Data de Publicação: 2021
Outros Autores: Cordoba-Granados, Juan J., Carabineiro, Sónia A. C., Gutierrez-Merino, Carlos, Aureliano, Manuel, Mata, Ana M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.1/17459
Resumo: Plasma 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.
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spelling Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viabilityGold compoundsPMCACa2+-ATPaseCalcium homeostasisSH-SY5Y human neuroblastoma cellsPlasma 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.Projects 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).MDPISapientiaBerrocal, MariaCordoba-Granados, Juan J.Carabineiro, Sónia A. C.Gutierrez-Merino, CarlosAureliano, ManuelMata, Ana M.2022-01-10T14:58:05Z2021-11-302021-12-23T15:06:53Z2021-11-30T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/17459engMetals 11 (12): 1934 (2021)2075-470110.3390/met11121934info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:29:34Zoai:sapientia.ualg.pt:10400.1/17459Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:07:23.633612Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability
title Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability
spellingShingle Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability
Berrocal, Maria
Gold compounds
PMCA
Ca2+-ATPase
Calcium homeostasis
SH-SY5Y human neuroblastoma cells
title_short Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability
title_full Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability
title_fullStr Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability
title_full_unstemmed Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability
title_sort Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability
author Berrocal, Maria
author_facet Berrocal, Maria
Cordoba-Granados, Juan J.
Carabineiro, Sónia A. C.
Gutierrez-Merino, Carlos
Aureliano, Manuel
Mata, Ana M.
author_role author
author2 Cordoba-Granados, Juan J.
Carabineiro, Sónia A. C.
Gutierrez-Merino, Carlos
Aureliano, Manuel
Mata, Ana M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Sapientia
dc.contributor.author.fl_str_mv Berrocal, Maria
Cordoba-Granados, Juan J.
Carabineiro, Sónia A. C.
Gutierrez-Merino, Carlos
Aureliano, Manuel
Mata, Ana M.
dc.subject.por.fl_str_mv Gold compounds
PMCA
Ca2+-ATPase
Calcium homeostasis
SH-SY5Y human neuroblastoma cells
topic Gold compounds
PMCA
Ca2+-ATPase
Calcium homeostasis
SH-SY5Y human neuroblastoma cells
description Plasma 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.
publishDate 2021
dc.date.none.fl_str_mv 2021-11-30
2021-12-23T15:06:53Z
2021-11-30T00:00:00Z
2022-01-10T14:58:05Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.1/17459
url http://hdl.handle.net/10400.1/17459
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Metals 11 (12): 1934 (2021)
2075-4701
10.3390/met11121934
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