Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , |
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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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 |
format |
article |
status_str |
publishedVersion |
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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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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MDPI |
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MDPI |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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