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Epithelial Cells
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
The cysteine protease, cathepsin B, has been detected in bronchoalveolar lavage fluids and sputum from patients with chronic bronchitis, bronchiectasis, and emphysema (252–254). Because this protease can hydrolyze extracellular matrix proteins (255), it could contribute to connective tissue damage in the airway. Cathepsin B is usually stored as an inactive proenzyme in the lysosomes of cells, and the proenzyme is activated upon exposure to alkaline pH conditions, probably by proteases in lung secretions. It has recently been reported that bronchial epithelial cells synthesize and secrete procathepsin B that can be activated by neutrophil elastase to the form of the active enzyme that is found in airway secretions (256).
Interaction of Amebas with Cells
Published in Roberto R. Kretschmer, Amebiasis: Infection and Disease by Entamoeba histolytica, 2020
Lushbaugh and co-workers62 associated the cytotoxic activity with a neutral thiol proteinase with molecular weight about 24 kDa, active on azocasein at pH 6. Such an activity had been previously described63 and was shown to be greater in the more virulent strains. The thiol proteinase described had a molecular weight of 16 kDa and was inhibited by leupeptin and serum and activated by free sulphydril groups so that it resembled cathepsin B. 61,64 A weakly acid or neutral thiol proteinase has been described by a number of groups.65-70 The reports vary as to the exact molecular weight of the protein but it seems likely that the denatured enzyme has a molecular weight of between 16 to 30 kDa and that higher molecular weight species represent artifacts of the gel procedures due to partially native forms.61,70 From the substrate preferences and N-terminal sequence61,67,70 the enzyme resembles but is not identical to cathepsin B.
Role of Mediators Released by Leukocytes During Liver Transplantation as Possible Contributing Factor for Hyperfibrinolysis and DIC
Published in Pia Glas-Greenwalt, Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
Cathepsin B is released from lysosomes of monocytes and macrophages,32 but may be released by hepatocytes, too.45 This cysteine proteinase has a broad unspecific proteolytic potency.32 In OLT, plasma levels of cathepsin B remained unchanged until the reperfusion phase (Figure 2). At that time, a highly significant increase became evident. Thereafter, cathepsin B decreased but remained elevated as compared with the preoperative levels until the end of the observation period. The maximum of cathepsin B immediately after revascularization in plasma reflects an excessive release of this lysosomal proteinase out of the graft as demonstrated by more than 100-fold higher levels in perfusate as compared with systemic blood at the end of the anhepatic phase.40
Macrophages in the reticuloendothelial system inhibit early induction stages of mouse apolipoprotein A-II amyloidosis
Published in Amyloid, 2023
Hiroki Miyahara, Jian Dai, Ying Li, Xiaoran Cui, Hibiki Takeuchi, Naomi Hachiya, Fuyuki Kametani, Masahide Yazaki, Masayuki Mori, Keiichi Higuchi
Based on our in vitro results, the proteolytic cleavage of AApoAII fibrils in lysosomes is one of the key processes for degradation. The inhibition of cathepsin B activity was critical for impairing the phagocytic degradation of internalized amyloid fibrils (Figure 3(I)). It is reported that autolysosomes are impaired in neurons before extracellular amyloid deposition in AD model mice [43]. Decreased levels of lysosome-associated proteins and impaired activity are observed in various cells of aged mice [44–46]. Moreover, young microglia-derived inflammatory factors enhance the proliferation and lysosomal activity of microglia, resulting in enhanced amyloid clearance properties [45]. Hence, there might be pathological mechanisms regarding the association between endosomal-lysosomal integrity and initiation of spontaneous AApoAII progression.
Drugs repurposing for SARS-CoV-2: new insight of COVID-19 druggability
Published in Expert Review of Anti-infective Therapy, 2022
Sujit Kumar Debnath, Monalisha Debnath, Rohit Srivastava, Abdelwahab Omri
This library also suggested some cysteine protease inhibitors like ONO 5334, VBY-825, ZLVG CHN2, and MDL-28170. Out of them, ONO 5334, VBY-825, and MDL 28170 are more potent against SARS-CoV-2. MDL-28170 is a cathepsin B inhibitor. Previously, this drug eradicated the infection caused by the Ebola virus and SARS-CoV. VBY-825 is a reversible cathepsin protease inhibitor, and ONO 5334 acts as a cathepsin K inhibitor. Human cysteinyl cathepsins are essential during infection for proteolytic processing of virally encoded proteins. Proper processing of S-protein is required to activate fusogenic activity where cathepsin activity is needed. The antiviral activity of MDL 28170 and ONO 5334 was evaluated in human induced pluripotent stem cells infected with SARS-CoV-2. Both drugs significantly reduced viral replication by 72% by ONO 5334 and 65% by MDL 28170 [106].
Porphyromonas gingivalis infection may contribute to systemic and intracerebral amyloid-beta: implications for Alzheimer’s disease onset
Published in Expert Review of Anti-infective Therapy, 2020
Another focus of Nie and colleagues [32] was Aβ1-42, which is classically considered as the toxic form of Aβ. They observed that Aβ3-42 (Figure 1) not only occurred earlier but was also two-fold higher than Aβ1-42 in the AD brain[32]. In AD, cathepsin B stimulated intracellular production of Aβ in the brain, including the Aβ3-42. Interestingly, Aβ3-42 following P.gingivalis-infection in mice generated IL-1β, which is a proinflammatory cytokine[32]. IL-1β participated in increasing the in vivo levels of Aβ3-42 in the hepatic macrophages of P.gingivalis-infected mice and in vitro P.gingivalis-infected macrophages. Furthermore, Aβ3-42 was induced by P.gingivalis infection, which had caused significant death of macrophages and reduced their phagocytic capacity compared to that of Aβ1-42, suggesting Aβ3-42 is very toxic. Aβ3-42 was also detected exclusively in the AD brain, and this corroborates with the significantly more toxic form than Aβ1-42[32]. This study agreed with that of Leira et al. [34] who reported that LPS from P.gingivalis increased Aβ protofibrils in the serum of rats. After experimental periodontitis had been induced in male Sprague-Dawley rats, it caused an acute elevation of Aβ1-40 in serum that lasted during the whole experiment. Aβ1-42 peptide levels, however, peaked at the end of the study.