Cathepsin B from bovine spleen

Cathepsin B from bovine spleen (Cathepsin B) is a member of the cysteine protease papain-like family. Cathepsin B is synthesized as a preproenzyme consisting of 335 amino acids, with a calculated molecular weight of approximately 36.7kDa. Cathepsin B is localized in the endosomal/lysosomal compartment, where Cathepsin B functions as both an endopeptidase and an exopeptidase. Cathepsin B primarily participates in the routine turnover of intracellular and extracellular proteins, thereby maintaining the homeostatic metabolic activity within the cell^[1]. Cathepsin B has three major subtypes, including the primary transcript, the primary transcript lacking exon 2, and the primary transcript lacking both exons 2 and 3 ^[2]. Cathepsin B may also regulate biological processes such as angiogenesis, cell invasion, tumor proliferation, immune resistance, neurogenesis, and cell differentiation. Cathepsin B is frequently associated with the development of inflammatory responses and cancer progression ^{[3, 4]}.

In vitro, Cathepsin B (10µg/mL) can be taken up by macrophages isolated from the bone marrow of C57Bl/6 mice, and it activates the activity of trypsin in macrophages while inducing inflammatory responses and cell death ^[5].

In vivo, Cathepsin B (115µg) was instilled into the lungs of hamsters. After 6 weeks, Cathepsin B induced the development of distorted alveolar focal areas and enlarged air space regions in the hamster lungs. Under the microscope, the lungs of hamsters treated with Cathepsin B showed a significantly higher number of secretory cells per millimeter of airway and a significant increase in the total number of cells per millimeter of airway ^[6-7].

References:
[1] Cavallo-Medved D, Moin K, Sloane B. Cathepsin B: Basis Sequence: Mouse. AFCS Nat Mol Pages. 2011;2011:A000508.
[2] Baudys M, Meloun B, Gan-Erdene T, et al. S-S bridges of cathepsin B and H from bovine spleen: a basis for cathepsin B model building and possible functional implications for discrimination between exo- and endopeptidase activities among cathepsins B, H and L. Biomed Biochim Acta. 1991;50(4-6):569-77.
[3] Mijanović O, Branković A, Panin AN, Savchuk S, Timashev P, Ulasov I, Lesniak MS. Cathepsin B: A sellsword of cancer progression. Cancer Lett. 2019 May 1;449:207-214.
[4] Brun S, Bestion E, Raymond E, et al. GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma via modulation of lysosomal functions. Autophagy. 2022 Mar;18(3):678-694..
[5] Sendler M, Weiss FU, Golchert J, et al. B-Mediated Activation of Trypsinogen in Endocytosing Macrophages Increases Severity of Pancreatitis in Mice. Gastroenterology. 2018 Feb;154(3):704-718.e10.
[6] Cardozo C, Padilla ML, Choi HS, et al. Goblet cell hyperplasia in large intrapulmonary airways after intratracheal injection of cathepsin B into hamsters. Am Rev Respir Dis. 1992 Mar;145(3):675-9.
[7] Lesser M, Padilla ML, Cardozo C. Induction of emphysema in hamsters by intratracheal instillation of cathepsin B. Am Rev Respir Dis. 1992 Mar;145(3):661-8.

Cathepsin B from bovine spleen（Cathepsin B）是半胱氨酸蛋白酶木瓜蛋白酶样家族的成员，合成为335个氨基酸的前酶原，计算分子量约为36.7kDa。Cathepsin B定位于内体/溶酶体区室，作为内肽酶和外肽酶发挥作用，主要参与细胞内和细胞外蛋白质的常规周转，从而维持细胞内的稳态代谢活性^[1]。Cathepsin B有3个主要的亚型，包括主转录本、缺乏外显子2的主转录本、缺乏外显子2和3的主转录本^[2]。Cathepsin B还可能调节血管生成、细胞侵袭、肿瘤增殖、免疫抵抗、神经发生、细胞分化等生物学过程，Cathepsin B常于炎症反应和癌症发展的发展联系在一起 ^{[3, 4]}。

在体外，Cathepsin B（10μg/mL）可被C57Bl/6小鼠的骨髓中分离出巨噬细胞吸收，并激活巨噬细胞中胰蛋白酶的活性，同时处境炎症反应和细胞死亡^[5]。

在体内，Cathepsin B（115μg）通过滴注到仓鼠的肺部，6周后，Cathepsin B诱导仓鼠的肺部出现扭曲的肺泡局灶区域、气腔区域扩大现象。同时在显微镜下，给予Cathepsin B处理的仓鼠大肺内气道每毫米气道含有显着更多的分泌细胞数量，每毫米气道总细胞数的显着增加^[6-7]。