Structural and functional properties of rBmTI-A: A Kunitz-BPTI serine protease inhibitor with therapeutical potential

Serine proteases are an important group of enzymes present in several organisms such as viruses, bacteria and eukaryotes involved in several physiological and pathological processes such as cancer, neurodegeneration, tissue inflammation and infections. Kunitz-type serine protease inhibitors have bee...

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Veröffentlicht in:Biochimie 2023-01, Vol.204, p.1-7
Hauptverfasser: Ferreira, Graziele Cristina, Bomediano Camillo, Lívia de Moraes, Sasaki, Sergio Daishi
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Sprache:eng
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Zusammenfassung:Serine proteases are an important group of enzymes present in several organisms such as viruses, bacteria and eukaryotes involved in several physiological and pathological processes such as cancer, neurodegeneration, tissue inflammation and infections. Kunitz-type serine protease inhibitors have been studied as therapeutical targets with positive results in many of these diseases. rBmTI-A (recombinant B. microplus Trypsin Inhibitor A) is a Kunitz-BPTI type inhibitor based on the native protein BmTI-A. BmTI-A was extracted from tick larvae and presented inhibitory activity against trypsin, human plasma kallikrein (HuPK), human neutrophil elastase (HNE) and human plasmin. rBmTI-A presented the same inhibitory activities of the BmTI-A and its thermostability has already been demonstrated. In emphysema induced by porcine pancreatic elastase (PPE) and by cigarette smoke animal models, the treatment using rBmTI-A showed a protective effect against the development of pulmonary emphysema and prevented the increase of inflammatory cells. In chronic allergic animal model, rBmTI-A treatment resulted in attenuated bronchial hyperresponsiveness, inflammation, remodeling. These are important physiological results in emphysema and lung inflammatory animal models with rBmTI-A treatment confirming its therapeutical potential. •rBmTI-A is a recombinant Kunitz-BPTI type inhibitor based on BmTI-A native protein.•rBmTI-A inhibit trypsin, human plasma kallikrein, human neutrophil elastase, plasmin.•rBmTI-A attenuated the development of pulmonary emphysema in mice.•rBmTI-A reduced the bronchial inflammation in chronic pulmonary inflammation model.•rBmTI-A inhibited viability of HUVEC cells in in vitro vessel formation assay.
ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2022.08.004