Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization
Main Author: | |
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Publication Date: | 2019 |
Other Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | eng |
Source: | Repositório Institucional da UNESP |
Download full: | http://dx.doi.org/10.3390/biom9080382 http://hdl.handle.net/11449/189728 |
Summary: | Thimet oligopeptidase (THOP1) is thought to be involved in neuropeptide metabolism, antigen presentation, neurodegeneration, and cancer. Herein, the generation of THOP1 C57BL/6 knockout mice (THOP1-/-) is described showing that they are viable, have estrus cycle, fertility, and a number of puppies per litter similar to C57BL/6 wild type mice (WT). In specific brain regions, THOP1-/- exhibit altered mRNA expression of proteasome beta5, serotonin 5HT2a receptor and dopamine D2 receptor, but not of neurolysin (NLN). Peptidomic analysis identifies differences in intracellular peptide ratios between THOP1-/- and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1-/- mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1-/- mice also exhibit better survival and improved behavior in a sepsis model, but also a greater peripheral pain sensitivity measured in the hot plate test after bradykinin administration in the paw. THOP1-/- mice show depressive-like behavior, as well as attention and memory retention deficits. Altogether, these results reveal a role of THOP1 on specific behaviors, immune-stimulated neurodegeneration, and infection-induced inflammation. |
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Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype CharacterizationinflammationMHC-IneurodegenerationpeptidomesepsisTHOP1Thimet oligopeptidase (THOP1) is thought to be involved in neuropeptide metabolism, antigen presentation, neurodegeneration, and cancer. Herein, the generation of THOP1 C57BL/6 knockout mice (THOP1-/-) is described showing that they are viable, have estrus cycle, fertility, and a number of puppies per litter similar to C57BL/6 wild type mice (WT). In specific brain regions, THOP1-/- exhibit altered mRNA expression of proteasome beta5, serotonin 5HT2a receptor and dopamine D2 receptor, but not of neurolysin (NLN). Peptidomic analysis identifies differences in intracellular peptide ratios between THOP1-/- and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1-/- mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1-/- mice also exhibit better survival and improved behavior in a sepsis model, but also a greater peripheral pain sensitivity measured in the hot plate test after bradykinin administration in the paw. THOP1-/- mice show depressive-like behavior, as well as attention and memory retention deficits. Altogether, these results reveal a role of THOP1 on specific behaviors, immune-stimulated neurodegeneration, and infection-induced inflammation.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo (USP), São Paulo 05508-000, SP, BrazilDepartment of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo 04023-062, SP, BrazilDepartment of Anatomy, Biomedical Sciences Institute, University of São Paulo (USP), São Paulo 05508-000, SP, BrazilDepartment of Pharmacology Faculty of Medicine of Ribeirao Preto University of São PauloDepartment of Psychobiology, Federal University of São Paulo (UNIFESP), São Paulo 04023-062, SP, BrazilDepartment of Pathology, Veterinarian Medical School, University of São Paulo (USP), São Paulo 05508-000, SP, BrazilSpecial Laboratory of Applied Toxinology (LETA) Center of Toxins Immune Response and Cell Signaling (CETICS) Butantan InstitutePharmacology Laboratory Butantan InstituteDepartment of Biophysics, Federal University of São Paulo (UNIFESP), São Paulo 04023-062, SP, BrazilMax-Delbrück-Center for Molecular MedicineCharité - Universitätsmedizin BerlinBerlin Institute of Health (BIH)DZHK (German Center for Cardiovascular Research), Partner Site BerlinInstitute for Biology University of LübeckBiosciences Institute, São Paulo State University (UNESP), 11330-900 São Vicente, SP, BrazilFAPESP: 2004/04933-2FAPESP: 2016/04000-3CNPq: 445363/2014-2, 400944/2014-6, 302809/2016-3, 150077/2015-7 and 449390-4Universidade de São Paulo (USP)Butantan InstituteMax-Delbrück-Center for Molecular MedicineCharité - Universitätsmedizin BerlinBerlin Institute of Health (BIH)DZHK (German Center for Cardiovascular Research)University of LübeckUniversidade Estadual Paulista (Unesp)Santos, Nilton B DosFranco, Roseane D.Camarini, RosanaMunhoz, Carolina D.Eichler, Rosangela A SGewehr, Mayara C FReckziegel, PatriciaLlanos, Ricardo P.Dale, Camila S.Silva, Victoria R O daBorges, Vanessa F.Lima, Braulio H FCunha, Fernando Q.Visniauskas, BrunaChagas, Jair R.Tufik, SergioPeres, Fernanda F.Abilio, Vanessa C.Florio, Jorge C.Iwai, Leo K.Rioli, VanessaPresoto, Benedito C.Guimaraes, Alessander O.Pesquero, Joao B.Bader, MichaelCastro, Leandro M.Ferro, Emer S.2019-10-06T16:50:16Z2019-10-06T16:50:16Z2019-08-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/biom9080382Biomolecules, v. 9, n. 8, 2019.2218-273Xhttp://hdl.handle.net/11449/18972810.3390/biom90803822-s2.0-85071533061Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBiomoleculesinfo:eu-repo/semantics/openAccess2021-10-23T04:16:07Zoai:repositorio.unesp.br:11449/189728Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T04:16:07Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization |
title |
Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization |
spellingShingle |
Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization Santos, Nilton B Dos inflammation MHC-I neurodegeneration peptidome sepsis THOP1 |
title_short |
Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization |
title_full |
Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization |
title_fullStr |
Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization |
title_full_unstemmed |
Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization |
title_sort |
Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization |
author |
Santos, Nilton B Dos |
author_facet |
Santos, Nilton B Dos Franco, Roseane D. Camarini, Rosana Munhoz, Carolina D. Eichler, Rosangela A S Gewehr, Mayara C F Reckziegel, Patricia Llanos, Ricardo P. Dale, Camila S. Silva, Victoria R O da Borges, Vanessa F. Lima, Braulio H F Cunha, Fernando Q. Visniauskas, Bruna Chagas, Jair R. Tufik, Sergio Peres, Fernanda F. Abilio, Vanessa C. Florio, Jorge C. Iwai, Leo K. Rioli, Vanessa Presoto, Benedito C. Guimaraes, Alessander O. Pesquero, Joao B. Bader, Michael Castro, Leandro M. Ferro, Emer S. |
author_role |
author |
author2 |
Franco, Roseane D. Camarini, Rosana Munhoz, Carolina D. Eichler, Rosangela A S Gewehr, Mayara C F Reckziegel, Patricia Llanos, Ricardo P. Dale, Camila S. Silva, Victoria R O da Borges, Vanessa F. Lima, Braulio H F Cunha, Fernando Q. Visniauskas, Bruna Chagas, Jair R. Tufik, Sergio Peres, Fernanda F. Abilio, Vanessa C. Florio, Jorge C. Iwai, Leo K. Rioli, Vanessa Presoto, Benedito C. Guimaraes, Alessander O. Pesquero, Joao B. Bader, Michael Castro, Leandro M. Ferro, Emer S. |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Butantan Institute Max-Delbrück-Center for Molecular Medicine Charité - Universitätsmedizin Berlin Berlin Institute of Health (BIH) DZHK (German Center for Cardiovascular Research) University of Lübeck Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Santos, Nilton B Dos Franco, Roseane D. Camarini, Rosana Munhoz, Carolina D. Eichler, Rosangela A S Gewehr, Mayara C F Reckziegel, Patricia Llanos, Ricardo P. Dale, Camila S. Silva, Victoria R O da Borges, Vanessa F. Lima, Braulio H F Cunha, Fernando Q. Visniauskas, Bruna Chagas, Jair R. Tufik, Sergio Peres, Fernanda F. Abilio, Vanessa C. Florio, Jorge C. Iwai, Leo K. Rioli, Vanessa Presoto, Benedito C. Guimaraes, Alessander O. Pesquero, Joao B. Bader, Michael Castro, Leandro M. Ferro, Emer S. |
dc.subject.por.fl_str_mv |
inflammation MHC-I neurodegeneration peptidome sepsis THOP1 |
topic |
inflammation MHC-I neurodegeneration peptidome sepsis THOP1 |
description |
Thimet oligopeptidase (THOP1) is thought to be involved in neuropeptide metabolism, antigen presentation, neurodegeneration, and cancer. Herein, the generation of THOP1 C57BL/6 knockout mice (THOP1-/-) is described showing that they are viable, have estrus cycle, fertility, and a number of puppies per litter similar to C57BL/6 wild type mice (WT). In specific brain regions, THOP1-/- exhibit altered mRNA expression of proteasome beta5, serotonin 5HT2a receptor and dopamine D2 receptor, but not of neurolysin (NLN). Peptidomic analysis identifies differences in intracellular peptide ratios between THOP1-/- and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1-/- mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1-/- mice also exhibit better survival and improved behavior in a sepsis model, but also a greater peripheral pain sensitivity measured in the hot plate test after bradykinin administration in the paw. THOP1-/- mice show depressive-like behavior, as well as attention and memory retention deficits. Altogether, these results reveal a role of THOP1 on specific behaviors, immune-stimulated neurodegeneration, and infection-induced inflammation. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-06T16:50:16Z 2019-10-06T16:50:16Z 2019-08-19 |
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://dx.doi.org/10.3390/biom9080382 Biomolecules, v. 9, n. 8, 2019. 2218-273X http://hdl.handle.net/11449/189728 10.3390/biom9080382 2-s2.0-85071533061 |
url |
http://dx.doi.org/10.3390/biom9080382 http://hdl.handle.net/11449/189728 |
identifier_str_mv |
Biomolecules, v. 9, n. 8, 2019. 2218-273X 10.3390/biom9080382 2-s2.0-85071533061 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Biomolecules |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1797789401361678336 |