Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization

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dc.contributor.authorSantos, Nilton B Dos
dc.contributor.authorFranco, Roseane D.
dc.contributor.authorCamarini, Rosana
dc.contributor.authorMunhoz, Carolina D.
dc.contributor.authorEichler, Rosangela A S
dc.contributor.authorGewehr, Mayara C F
dc.contributor.authorReckziegel, Patricia
dc.contributor.authorLlanos, Ricardo P.
dc.contributor.authorDale, Camila S.
dc.contributor.authorSilva, Victoria R O da
dc.contributor.authorBorges, Vanessa F.
dc.contributor.authorLima, Braulio H F
dc.contributor.authorCunha, Fernando Q.
dc.contributor.authorVisniauskas, Bruna
dc.contributor.authorChagas, Jair R.
dc.contributor.authorTufik, Sergio
dc.contributor.authorPeres, Fernanda F.
dc.contributor.authorAbilio, Vanessa C.
dc.contributor.authorFlorio, Jorge C.
dc.contributor.authorIwai, Leo K.
dc.contributor.authorRioli, Vanessa
dc.contributor.authorPresoto, Benedito C.
dc.contributor.authorGuimaraes, Alessander O.
dc.contributor.authorPesquero, Joao B.
dc.contributor.authorBader, Michael
dc.contributor.authorCastro, Leandro M.
dc.contributor.authorFerro, Emer S.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionButantan Institute
dc.contributor.institutionMax-Delbrück-Center for Molecular Medicine
dc.contributor.institutionCharité - Universitätsmedizin Berlin
dc.contributor.institutionBerlin Institute of Health (BIH)
dc.contributor.institutionDZHK (German Center for Cardiovascular Research)
dc.contributor.institutionUniversity of Lübeck
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2019-10-06T16:50:16Z
dc.date.available2019-10-06T16:50:16Z
dc.date.issued2019-08-19
dc.description.abstractThimet 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.en
dc.description.affiliationDepartment of Pharmacology, Biomedical Sciences Institute, University of São Paulo (USP), São Paulo 05508-000, SP, Brazil
dc.description.affiliationDepartment of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo 04023-062, SP, Brazil
dc.description.affiliationDepartment of Anatomy, Biomedical Sciences Institute, University of São Paulo (USP), São Paulo 05508-000, SP, Brazil
dc.description.affiliationDepartment of Pharmacology Faculty of Medicine of Ribeirao Preto University of São Paulo
dc.description.affiliationDepartment of Psychobiology, Federal University of São Paulo (UNIFESP), São Paulo 04023-062, SP, Brazil
dc.description.affiliationDepartment of Pathology, Veterinarian Medical School, University of São Paulo (USP), São Paulo 05508-000, SP, Brazil
dc.description.affiliationSpecial Laboratory of Applied Toxinology (LETA) Center of Toxins Immune Response and Cell Signaling (CETICS) Butantan Institute
dc.description.affiliationPharmacology Laboratory Butantan Institute
dc.description.affiliationDepartment of Biophysics, Federal University of São Paulo (UNIFESP), São Paulo 04023-062, SP, Brazil
dc.description.affiliationMax-Delbrück-Center for Molecular Medicine
dc.description.affiliationCharité - Universitätsmedizin Berlin
dc.description.affiliationBerlin Institute of Health (BIH)
dc.description.affiliationDZHK (German Center for Cardiovascular Research), Partner Site Berlin
dc.description.affiliationInstitute for Biology University of Lübeck
dc.description.affiliationBiosciences Institute, São Paulo State University (UNESP), 11330-900 São Vicente, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPESP: 2004/04933-2
dc.description.sponsorshipIdFAPESP: 2016/04000-3
dc.description.sponsorshipIdCNPq: 445363/2014-2, 400944/2014-6, 302809/2016-3, 150077/2015-7 and 449390-4
dc.identifierhttp://dx.doi.org/10.3390/biom9080382
dc.identifier.citationBiomolecules, v. 9, n. 8, 2019.
dc.identifier.doi10.3390/biom9080382
dc.identifier.issn2218-273X
dc.identifier.scopus2-s2.0-85071533061
dc.identifier.urihttp://hdl.handle.net/11449/189728
dc.language.isoeng
dc.relation.ispartofBiomolecules
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectinflammation
dc.subjectMHC-I
dc.subjectneurodegeneration
dc.subjectpeptidome
dc.subjectsepsis
dc.subjectTHOP1
dc.titleThimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterizationen
dc.typeArtigo

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Artigos - Patologia - FMB
Artigos - Ciências Biológicas - São Vicente