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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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dos Santos, Nilton B. [1] ; Franco, Roseane D. [1] ; Camarini, Rosana [1] ; Munhoz, Carolina D. [1] ; Eichler, Rosangela A. S. [1] ; Gewehr, Mayara C. F. [1] ; Reckziegel, Patricia [1, 2] ; Llanos, Ricardo P. [1] ; Dale, Camila S. [3] ; da Silva, Victoria R. O. [3] ; Borges, Vanessa F. [4] ; Lima, Braulio H. F. [4] ; Cunha, Fernando Q. [4] ; Visniauskas, Bruna [5] ; Chagas, Jair R. [5] ; Tufik, Sergio [5] ; Peres, Fernanda F. [2] ; Abilio, Vanessa C. [2] ; Florio, Jorge C. [6] ; Iwai, Leo K. [7] ; Rioli, Vanessa [7] ; Presoto, Benedito C. [8] ; Guimaraes, Alessander O. [9] ; Pesquero, Joao B. [9] ; Bader, Michael [10, 11, 12, 13, 14] ; Castro, Leandro M. [15] ; Ferro, Emer S. [1]
Total Authors: 27
Affiliation:
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[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508000 Sao Paulo, SP - Brazil
[2] Fed Univ Sao Paulo UNIFESP, Dept Pharmacol, BR-04023062 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508000 Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil
[5] Fed Univ Sao Paulo UNIFESP, Dept Psychobiol, BR-04023062 Sao Paulo - Brazil
[6] Univ Sao Paulo, Vet Med Sch, Dept Pathol, BR-05508000 Sao Paulo, SP - Brazil
[7] Butantan Inst, Ctr Toxins Immune Response & Cell Signaling CETIC, Special Lab Appl Toxinol LETA, BR-05503900 Sao Paulo - Brazil
[8] Butantan Inst, Pharmacol Lab, BR-05503900 Sao Paulo - Brazil
[9] Fed Univ Sao Paulo UNIFESP, Dept Biophys, BR-04023062 Sao Paulo, SP - Brazil
[10] Max Delbruck Ctr Mol Med, D-13125 Berlin - Germany
[11] Charite Univ Med Berlin, D-13353 Berlin - Germany
[12] BIH, D-10117 Berlin - Germany
[13] DZHK German Ctr Cardiovasc Res, Partner Site Berlin, D-10785 Berlin - Germany
[14] Univ Lubeck, Inst Biol, D-23538 Lubeck - Germany
[15] Sao Paulo State Univ UNESP, Biosci Inst, BR-11330900 Sao Vicente, SP - Brazil
Total Affiliations: 15
Document type: Journal article
Source: BIOMOLECULES; v. 9, n. 8 AUG 2019.
Web of Science Citations: 0
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. (AU)

FAPESP's process: 16/04000-3 - Pharmacology of oligopeptidases and intracellular peptides
Grantee:Emer Suavinho Ferro
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 15/07273-8 - Molecular mechanism of intracellular peptides on gene expression and signaling in skeletal muscle model
Grantee:Ricardo Pariona Llanos
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 04/04933-2 - Molecular cell biology of oligopeptidases
Grantee:Emer Suavinho Ferro
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 15/20657-0 - Evaluation of hemopressin (HP) pharmacological use on obesity treatment
Grantee:Patrícia Reckziegel
Support Opportunities: Scholarships in Brazil - Post-Doctoral