Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell Line
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/10316/103760 https://doi.org/10.3390/biomedicines9070777 |
Resumo: | The signaling pathways involved in age-related inflammation are increasingly recognized as targets for the development of preventive and therapeutic strategies. Our previous study elucidated the structure-activity relationship of monoterpene compounds derived from p-menthane as potential anti-inflammatory drugs and identified (S)-(+)-carvone as the most potent among the compounds tested. This study aims at identifying the molecular mechanism underlying the anti-inflammatory properties of (S)-(+)-carvone. The murine macrophage cell line, Raw 264.7, was stimulated with bacterial lipopolysaccharide (LPS) to simulate inflammation. Western blot was used to assess protein levels and post-translational modifications. The subcellular localization of NF-κB/p65 was visualized by immunocytochemistry. An in vitro fluorometric assay was used to measure Sirtuin-1 (SIRT1) activity. (S)-(+)-carvone inhibited LPS-induced JNK1 phosphorylation, but not that of p38 and ERK1/2 and also did not affect the phosphorylation and degradation of the NF-κB inhibitor, IκB-α. Accordingly, (S)-(+)-carvone did not affect LPS-induced phosphorylation of NF-κB/p65 on Ser536 and its nuclear translocation, but it significantly decreased LPS-induced IκB-α resynthesis, a NF-κB-dependent process, and NF-κB/p65 acetylation on lysine (Lys) 310. Deacetylation of that Lys residue is dependent on the activity of SIRT1, which was found to be increased by (S)-(+)-carvone, while its protein levels were unaffected. Taken together, these results show that (S)-(+)-carvone is a new SIRT1 activator with the potential to counteract the chronic low-grade inflammation characteristic of age-related diseases. |
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Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell LineaginginflammationmonoterpeneNF- BSirtuin-1Sirtuin-1 activating compoundThe signaling pathways involved in age-related inflammation are increasingly recognized as targets for the development of preventive and therapeutic strategies. Our previous study elucidated the structure-activity relationship of monoterpene compounds derived from p-menthane as potential anti-inflammatory drugs and identified (S)-(+)-carvone as the most potent among the compounds tested. This study aims at identifying the molecular mechanism underlying the anti-inflammatory properties of (S)-(+)-carvone. The murine macrophage cell line, Raw 264.7, was stimulated with bacterial lipopolysaccharide (LPS) to simulate inflammation. Western blot was used to assess protein levels and post-translational modifications. The subcellular localization of NF-κB/p65 was visualized by immunocytochemistry. An in vitro fluorometric assay was used to measure Sirtuin-1 (SIRT1) activity. (S)-(+)-carvone inhibited LPS-induced JNK1 phosphorylation, but not that of p38 and ERK1/2 and also did not affect the phosphorylation and degradation of the NF-κB inhibitor, IκB-α. Accordingly, (S)-(+)-carvone did not affect LPS-induced phosphorylation of NF-κB/p65 on Ser536 and its nuclear translocation, but it significantly decreased LPS-induced IκB-α resynthesis, a NF-κB-dependent process, and NF-κB/p65 acetylation on lysine (Lys) 310. Deacetylation of that Lys residue is dependent on the activity of SIRT1, which was found to be increased by (S)-(+)-carvone, while its protein levels were unaffected. Taken together, these results show that (S)-(+)-carvone is a new SIRT1 activator with the potential to counteract the chronic low-grade inflammation characteristic of age-related diseases.2021-07-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/103760http://hdl.handle.net/10316/103760https://doi.org/10.3390/biomedicines9070777eng2227-9059Sousa, CátiaNeves, Bruno MiguelLeitão, Alcino JorgeMendes, Alexandrina Ferreirainfo: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:RCAAP2022-11-25T21:37:22Zoai:estudogeral.uc.pt:10316/103760Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:20:32.379456Repositório 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 |
Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell Line |
title |
Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell Line |
spellingShingle |
Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell Line Sousa, Cátia aging inflammation monoterpene NF- B Sirtuin-1 Sirtuin-1 activating compound |
title_short |
Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell Line |
title_full |
Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell Line |
title_fullStr |
Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell Line |
title_full_unstemmed |
Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell Line |
title_sort |
Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell Line |
author |
Sousa, Cátia |
author_facet |
Sousa, Cátia Neves, Bruno Miguel Leitão, Alcino Jorge Mendes, Alexandrina Ferreira |
author_role |
author |
author2 |
Neves, Bruno Miguel Leitão, Alcino Jorge Mendes, Alexandrina Ferreira |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Sousa, Cátia Neves, Bruno Miguel Leitão, Alcino Jorge Mendes, Alexandrina Ferreira |
dc.subject.por.fl_str_mv |
aging inflammation monoterpene NF- B Sirtuin-1 Sirtuin-1 activating compound |
topic |
aging inflammation monoterpene NF- B Sirtuin-1 Sirtuin-1 activating compound |
description |
The signaling pathways involved in age-related inflammation are increasingly recognized as targets for the development of preventive and therapeutic strategies. Our previous study elucidated the structure-activity relationship of monoterpene compounds derived from p-menthane as potential anti-inflammatory drugs and identified (S)-(+)-carvone as the most potent among the compounds tested. This study aims at identifying the molecular mechanism underlying the anti-inflammatory properties of (S)-(+)-carvone. The murine macrophage cell line, Raw 264.7, was stimulated with bacterial lipopolysaccharide (LPS) to simulate inflammation. Western blot was used to assess protein levels and post-translational modifications. The subcellular localization of NF-κB/p65 was visualized by immunocytochemistry. An in vitro fluorometric assay was used to measure Sirtuin-1 (SIRT1) activity. (S)-(+)-carvone inhibited LPS-induced JNK1 phosphorylation, but not that of p38 and ERK1/2 and also did not affect the phosphorylation and degradation of the NF-κB inhibitor, IκB-α. Accordingly, (S)-(+)-carvone did not affect LPS-induced phosphorylation of NF-κB/p65 on Ser536 and its nuclear translocation, but it significantly decreased LPS-induced IκB-α resynthesis, a NF-κB-dependent process, and NF-κB/p65 acetylation on lysine (Lys) 310. Deacetylation of that Lys residue is dependent on the activity of SIRT1, which was found to be increased by (S)-(+)-carvone, while its protein levels were unaffected. Taken together, these results show that (S)-(+)-carvone is a new SIRT1 activator with the potential to counteract the chronic low-grade inflammation characteristic of age-related diseases. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-07-04 |
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/10316/103760 http://hdl.handle.net/10316/103760 https://doi.org/10.3390/biomedicines9070777 |
url |
http://hdl.handle.net/10316/103760 https://doi.org/10.3390/biomedicines9070777 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2227-9059 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134097800429568 |