Ferreira Graziele Cristina, Bomediano Camillo Lívia de Moraes, Sasaki Sergio Daishi
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC - UFABC, São Bernardo do Campo, São Paulo, Brazil; Graduate Program on Biosystems, Federal University of ABC, São Bernardo do Campo, São Paulo, Brazil.
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC - UFABC, São Bernardo do Campo, São Paulo, Brazil; Graduate Program on Biosystems, Federal University of ABC, São Bernardo do Campo, São Paulo, Brazil.
Biochimie. 2023 Jan;204:1-7. doi: 10.1016/j.biochi.2022.08.004. Epub 2022 Aug 28.
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.
丝氨酸蛋白酶是一类重要的酶，存在于多种生物体中，如病毒、细菌和真核生物，参与多种生理和病理过程，如癌症、神经退行性变、组织炎症和感染。Kunitz型丝氨酸蛋白酶抑制剂已作为治疗靶点进行研究，并在许多此类疾病中取得了积极成果。rBmTI-A（重组微小牛蜱胰蛋白酶抑制剂A）是一种基于天然蛋白BmTI-A的Kunitz-BPTI型抑制剂。BmTI-A是从蜱幼虫中提取的，对胰蛋白酶、人血浆激肽释放酶（HuPK）、人中性粒细胞弹性蛋白酶（HNE）和人纤溶酶具有抑制活性。rBmTI-A具有与BmTI-A相同的抑制活性，并且其热稳定性已经得到证实。在猪胰弹性蛋白酶（PPE）和香烟烟雾诱导的肺气肿动物模型中，使用rBmTI-A进行治疗对肺气肿的发展显示出保护作用，并防止了炎症细胞的增加。在慢性过敏性动物模型中，rBmTI-A治疗导致支气管高反应性、炎症和重塑减轻。这些是rBmTI-A治疗在肺气肿和肺部炎症动物模型中的重要生理结果，证实了其治疗潜力。
