Thimet oligopeptidase (EC 3.4.24.15) key functions suggested by knockout mice phenotype characterization
| Autor: | Roseane D. Franco, Alessander O. Guimaraes, Rosangela Aparecida dos Santos Eichler, Ricardo Pariona Llanos, Jorge Camilo Flório, Rosana Camarini, Nilton Barreto dos Santos, Sergio Tufik, Bruna Visniauskas, Braulio H.F. Lima, Camila Squarzoni Dale, Vanessa C. Abílio, Mayara C. F. Gewehr, Benedito C. Presoto, Vanessa Rioli, Vanessa F. Borges, Leandro M. Castro, Michael Bader, João Bosco Pesquero, Fernanda Fiel Peres, Carolina Demarchi Munhoz, Jair R. Chagas, Fernando Q. Cunha, Victoria R. O. da Silva, Emer S. Ferro, Patrícia Reckziegel, Leo Kei Iwai |
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| Přispěvatelé: | 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) |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty 5-HT2A receptor lcsh:QR1-502 Neuropeptide Biology Biochemistry Article lcsh:Microbiology sepsis Mice 03 medical and health sciences 0302 clinical medicine Dopamine receptor D2 Internal medicine parasitic diseases MHC-I peptidome medicine Animals Hot plate test Molecular Biology Mice Knockout Thimet oligopeptidase Behavior Animal FENÓTIPOS Neurodegeneration neurodegeneration Metalloendopeptidases medicine.disease Mice Inbred C57BL Phenotype 030104 developmental biology Endocrinology inflammation Cardiovascular and Metabolic Diseases Knockout mouse Female Serotonin THOP1 030217 neurology & neurosurgery |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Biomolecules, Vol 9, Iss 8, p 382 (2019) Biomolecules Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP Volume 9 Issue 8 |
| Popis: | 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&minus /&minus ) 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. |
| Databáze: | OpenAIRE |
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