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| Item Type: | Article |
|---|---|
| Title: | Thimet oligopeptidase (EC 3.4.24.15) key functions suggested by knockout mice phenotype characterization |
| Creators Name: | Santos, N.B.D., Franco, R.D., Camarini, R., Munhoz, C.D., Eichler, R.A.S., Gewehr, M.C.F., Reckziegel, P., Llanos, R.P., Dale, C.S., da Silva, V.R.O., Borges, V.F., Lima, B.H.F., Cunha, F.Q., Visniauskas, B., Chagas, J.R., Tufik, S., Peres, F.F., Abilio, V.C., Florio, J.C., Iwai, L.K., Rioli, V., Presoto, B.C., Guimaraes, A.O., Pesquero, J.B., Bader, M., Castro, L.M. and Ferro, E.S. |
| Abstract: | 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. |
| Keywords: | THOP1, Neurodegeneration, Inflammation, Sepsis, MHC-I, Peptidome, Animals, Mice |
| Source: | Biomolecules |
| ISSN: | 2218-273X |
| Publisher: | MDPI |
| Volume: | 9 |
| Number: | 8 |
| Page Range: | 382 |
| Date: | 19 August 2019 |
| Official Publication: | https://doi.org/10.3390/biom9080382 |
| PubMed: | View item in PubMed |
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