Lupinus albus protein componentes inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivo
Autor(a) principal: | |
---|---|
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/10400.5/22755 |
Resumo: | Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are regarded as important clinical targets due to their nodal-point role in inflammatory and oncological diseases. Here, we aimed at isolating and characterizing am MMP-2 and-9 inhibitor (MMPI) from Lupinus albus and at assessing its efficacy in vitro and in vivo. The protein was isolated using chromatographic and 2-D electrophoretic procedures and sequenced by using MALDI-TOF TOF and MS/MS analysis. In vitro MMP-2 and 9 inhibitions were determined on colon adenocarcinoma (HT29) cells, as well as by measuring the expression levels of genes related to these enzymes. Inhibitory activities were also confirmed in vivo using a model of experimental TNBS-induced colitis in mice, with oral administrations of 15 mg kg1. After chromatographic and electrophoretic isolation, the L. albus MMP-9 inhibitor was found to comprise a large fragment from -conglutin and, to a lower extent, small fragments of -conglutin. In vitro studies showed that the MMPI successfully inhibited MMP-9 activity in a dose-dependent manner in colon cancer cells, with an IC50 of 10 g mL1 without impairing gene expression nor cell growth. In vivo studies showed that the MMPI maintained its bioactivities when administered orally and significantly reduced colitis symptoms, along with a very significant inhibition of MMP-2 and -9 activities. Overall, results reveal a novel type of MMPI in lupine that is edible, proteinaceous in nature and soluble in water, and effective in vivo, suggesting a high potential application as a nutraceutical or a functional food in pathologies related to abnormally high MMP-9 activity in the digestive system |
id |
RCAP_7d9799299112b7bcc1ec3b7614b749b3 |
---|---|
oai_identifier_str |
oai:www.repository.utl.pt:10400.5/22755 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Lupinus albus protein componentes inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivoLupinus albus proteinMMP-9MMP-2gelatinasesMMP inhibitornutraceuticalgastrointestinal diseasesMatrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are regarded as important clinical targets due to their nodal-point role in inflammatory and oncological diseases. Here, we aimed at isolating and characterizing am MMP-2 and-9 inhibitor (MMPI) from Lupinus albus and at assessing its efficacy in vitro and in vivo. The protein was isolated using chromatographic and 2-D electrophoretic procedures and sequenced by using MALDI-TOF TOF and MS/MS analysis. In vitro MMP-2 and 9 inhibitions were determined on colon adenocarcinoma (HT29) cells, as well as by measuring the expression levels of genes related to these enzymes. Inhibitory activities were also confirmed in vivo using a model of experimental TNBS-induced colitis in mice, with oral administrations of 15 mg kg1. After chromatographic and electrophoretic isolation, the L. albus MMP-9 inhibitor was found to comprise a large fragment from -conglutin and, to a lower extent, small fragments of -conglutin. In vitro studies showed that the MMPI successfully inhibited MMP-9 activity in a dose-dependent manner in colon cancer cells, with an IC50 of 10 g mL1 without impairing gene expression nor cell growth. In vivo studies showed that the MMPI maintained its bioactivities when administered orally and significantly reduced colitis symptoms, along with a very significant inhibition of MMP-2 and -9 activities. Overall, results reveal a novel type of MMPI in lupine that is edible, proteinaceous in nature and soluble in water, and effective in vivo, suggesting a high potential application as a nutraceutical or a functional food in pathologies related to abnormally high MMP-9 activity in the digestive systemMDPIRepositório da Universidade de LisboaMota, JoanaDireito, RosaRocha, JoãoFernandes, JoãoSepodes, BrunoFigueira, Maria EduardoRaymundo, AnabelaLima, AnaFerreira, Ricardo Boavida2021-12-17T10:15:42Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.5/22755engMota, J.; Direito, R.; Rocha, J.; Fernandes, J.; Sepodes, B.; Figueira, M.E.; Raymundo, A.; Lima, A.; Ferreira, R.B. Lupinus albus Protein Components Inhibit MMP-2 and MMP-9 Gelatinolytic Activity In Vitro and In Vivo. Int. J. Mol. Sci. 2021, 22, 13286https://doi.org/10.3390/ ijms222413286info: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:RCAAP2023-03-06T14:52:18Zoai:www.repository.utl.pt:10400.5/22755Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:07:05.885321Repositório 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 |
Lupinus albus protein componentes inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivo |
title |
Lupinus albus protein componentes inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivo |
spellingShingle |
Lupinus albus protein componentes inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivo Mota, Joana Lupinus albus protein MMP-9 MMP-2 gelatinases MMP inhibitor nutraceutical gastrointestinal diseases |
title_short |
Lupinus albus protein componentes inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivo |
title_full |
Lupinus albus protein componentes inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivo |
title_fullStr |
Lupinus albus protein componentes inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivo |
title_full_unstemmed |
Lupinus albus protein componentes inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivo |
title_sort |
Lupinus albus protein componentes inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivo |
author |
Mota, Joana |
author_facet |
Mota, Joana Direito, Rosa Rocha, João Fernandes, João Sepodes, Bruno Figueira, Maria Eduardo Raymundo, Anabela Lima, Ana Ferreira, Ricardo Boavida |
author_role |
author |
author2 |
Direito, Rosa Rocha, João Fernandes, João Sepodes, Bruno Figueira, Maria Eduardo Raymundo, Anabela Lima, Ana Ferreira, Ricardo Boavida |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Mota, Joana Direito, Rosa Rocha, João Fernandes, João Sepodes, Bruno Figueira, Maria Eduardo Raymundo, Anabela Lima, Ana Ferreira, Ricardo Boavida |
dc.subject.por.fl_str_mv |
Lupinus albus protein MMP-9 MMP-2 gelatinases MMP inhibitor nutraceutical gastrointestinal diseases |
topic |
Lupinus albus protein MMP-9 MMP-2 gelatinases MMP inhibitor nutraceutical gastrointestinal diseases |
description |
Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are regarded as important clinical targets due to their nodal-point role in inflammatory and oncological diseases. Here, we aimed at isolating and characterizing am MMP-2 and-9 inhibitor (MMPI) from Lupinus albus and at assessing its efficacy in vitro and in vivo. The protein was isolated using chromatographic and 2-D electrophoretic procedures and sequenced by using MALDI-TOF TOF and MS/MS analysis. In vitro MMP-2 and 9 inhibitions were determined on colon adenocarcinoma (HT29) cells, as well as by measuring the expression levels of genes related to these enzymes. Inhibitory activities were also confirmed in vivo using a model of experimental TNBS-induced colitis in mice, with oral administrations of 15 mg kg1. After chromatographic and electrophoretic isolation, the L. albus MMP-9 inhibitor was found to comprise a large fragment from -conglutin and, to a lower extent, small fragments of -conglutin. In vitro studies showed that the MMPI successfully inhibited MMP-9 activity in a dose-dependent manner in colon cancer cells, with an IC50 of 10 g mL1 without impairing gene expression nor cell growth. In vivo studies showed that the MMPI maintained its bioactivities when administered orally and significantly reduced colitis symptoms, along with a very significant inhibition of MMP-2 and -9 activities. Overall, results reveal a novel type of MMPI in lupine that is edible, proteinaceous in nature and soluble in water, and effective in vivo, suggesting a high potential application as a nutraceutical or a functional food in pathologies related to abnormally high MMP-9 activity in the digestive system |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-12-17T10:15:42Z 2021 2021-01-01T00:00:00Z |
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/10400.5/22755 |
url |
http://hdl.handle.net/10400.5/22755 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Mota, J.; Direito, R.; Rocha, J.; Fernandes, J.; Sepodes, B.; Figueira, M.E.; Raymundo, A.; Lima, A.; Ferreira, R.B. Lupinus albus Protein Components Inhibit MMP-2 and MMP-9 Gelatinolytic Activity In Vitro and In Vivo. Int. J. Mol. Sci. 2021, 22, 13286 https://doi.org/10.3390/ ijms222413286 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
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 |
|
_version_ |
1799131163890024448 |