title: BmTI-A, a Kunitz type inhibitor from Rhipicephalus microplus able to interfere in vessel formation.
abstract: Rhipicephalus microplus is an ectoparasite responsible for transmissions of babesiosis and anaplasmosis causing large losses to livestock production. To survive R. microplus tick produces several active molecules, such as protease inhibitors. This ectoparasite has been described as a rich source of serine protease inhibitors most of them are Kunitz-BPTI members named BmTIs which have no clear function yet. In the present work, we described the expression and functional characterization of rBmTI-A which showed to be similar to the native BmTI-A, a double-headed Kunitz-BPTI inhibitor, capable to inhibit trypsin, human neutrophil elastase (HNE), human plasma kalikrein (HuPK) and human plasmin. rBmTI-A was able to cause a decrease of HUVEC cell viability. Besides, the rBmTI-A showed to be a potent inhibitor of "in vitro" vessel formation. Our results suggested that BmTI-A may participate in the blood acquisition process interfering in the vessel formation during the tick parasite life stage, around 20 days. In conclusion, BmTI-A is a promising molecule to be used in the drug design and development of new method of R. microplus control.
authors.affiliation: Department of Biochemistry, Escola Paulista de Medicina, Universidade de Federal de São Paulo (UNIFESP), Rua 3 de Maio 100, 04044-020 São Paulo, SP, Brazil.
authors.forename: Tatiane S
authors.initials: TS
authors.lastname: Soares
authors.affiliation: Department of Biochemistry, Escola Paulista de Medicina, Universidade de Federal de São Paulo (UNIFESP), Rua 3 de Maio 100, 04044-020 São Paulo, SP, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Oliveira
authors.affiliation: Department of Biochemistry, Escola Paulista de Medicina, Universidade de Federal de São Paulo (UNIFESP), Rua 3 de Maio 100, 04044-020 São Paulo, SP, Brazil.
authors.forename: Ricardo J S
authors.initials: RJ
authors.lastname: Torquato
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Rua Catequese, 242, 09090-400 Santo André, SP, Brazil.
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Sasaki
authors.affiliation: Department of Biochemistry, Escola Paulista de Medicina, Universidade de Federal de São Paulo (UNIFESP), Rua 3 de Maio 100, 04044-020 São Paulo, SP, Brazil.
authors.forename: Mariana S
authors.initials: MS
authors.lastname: Araujo
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade de Federal de São Paulo (UNIFESP), 04023-062 São Paulo, SP, Brazil.
authors.forename: Thaysa
authors.initials: T
authors.lastname: Paschoalin
authors.affiliation: Department of Biochemistry, Escola Paulista de Medicina, Universidade de Federal de São Paulo (UNIFESP), Rua 3 de Maio 100, 04044-020 São Paulo, SP, Brazil. Electronic address: tanaka.bioq@epm.br.
authors.forename: Aparecida S
authors.initials: AS
authors.lastname: Tanaka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004798:Enzymes / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D023061:Gene Order; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D048494:Rhipicephalus / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D059467:Transcriptome
chemical_list: D004798:Enzymes; D015842:Serine Proteinase Inhibitors
keywords: Angiogenesis; Kallikrein; Kunitz; Plasmin; Protease inhibitor; Rhipicephalus microplus; Tick