-Glutamic Acid): Efficient Carrier of Cancer Therapeutics and Diagnostics
Mansoor M. Amiji in Nanotechnology for Cancer Therapy, 2006
The enzymatic degradability of PG–drug conjugates is influenced by their structure, composition, and charge as well as the physicochemical properties of the drug attached to PG.22–25 PG is more susceptible to lysosomal degradation than are poly(aspartic acid) and poly(d-glutamic acid).26 Cysteine proteases, particularly cathepsin B, play key roles in the lysosomal degradation of PG.22,27 Although researchers have identified oligomeric glutamic acids as the primary degradation products of PG,28 more recent results demonstrated that monomeric L-glutamic acid is produced in the lysosomal degradation of PG.29 Degradation of the PG backbone may not necessarily lead to the release of free drug in every case.
Mechanisms of Tumor Cell Invasion studied In Vitro
Rolf Bjerkvig in Spheroid Culture in Cancer Research, 2017
Because of the complexity of the various extracellular matrices in different tissues, metastasis succeeds only by virtue of a diversity of enzymes capable of digesting different matrix components.19 The spectrum of proteases is broad and includes enzymes that recognize as substrate each of the components of the basal lamina.22,23 These enzymes include serine-, thiol-, and metalloproteases, which operate with pH optima between 6.5 and 8.5. Additionally, cathepsin B has been found to be localized in the plasma membrane of metastatic cells.26 Because the pH optimum of cathepsin B is between 6.0 to 6.5, it is speculated that the local environment of invading tumor cells may be altered by way of regional acidity in order to accommodate restrictions on enzyme function.21
Interaction of Amebas with Cells
Roberto R. Kretschmer in 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.
Nasal mucus proteome and its involvement in allergic rhinitis
Published in Expert Review of Proteomics, 2020
Peter Valentin Tomazic, Barbara Darnhofer, Ruth Birner-Gruenberger
Pollen proteases can degrade tight junctions [57] and subsequently harm the nasal epithelium. One hypothesis is that an imbalance of nasal mucus antiproteases could favor protease activity and influence the disease. Hamaguchi et al. [23] found that protease activity in acute sinusitis was high, potentially hampering the healing process, whereas in allergic rhinitis protease activity in mucus was weak. They only focused on functional activity of cathepsin B and L, both cysteine proteases, while distinct antiproteases and their potential functional defects were not addressed. Belkowski et al. [58] investigated secretory leukocyte protease inhibitor (SLPI), which is cleaved by chymase. SLPIs, as well as elafin, are potent serine protease inhibitors. SLPI inhibits cathepsin G and elastase whereas elafin inhibits elastase and proteinase 3 but not cathepsin G. Cathepsin G is a serine protease with bactericidal function through hydrolytic degradation of bacteria and extracellular matrix components. This mechanism cannot be completely hampered by protease inhibitors [51,59]. SLPI and elafin were found in epithelium and mucus of the upper respiratory tract. They have antibacterial and antifungal properties and are up-regulated during inflammatory processes. The ratio between the native and the cleaved form of SLPI reflects inflammatory activity, but its involvement in the pathophysiology of the disease has not been elucidated.
Smart albumin-loaded Rose Bengal and doxorubicin nanoparticles for breast cancer therapy
Published in Journal of Microencapsulation, 2019
Jing Sun, Li Zhang, Ying Zhang, Chun-Wen Yue, Jia Lin, Haisheng Wang, Zeng-Jun Fang, Jing Wu
The microenvironment of cancer is varied from normal tissues, mainly characterised by acidic, up-regulated enzyme expression, and temperature sensitivity. These alterations can be employed to design smart targeting agents. The expression of cathepsin B increases and plays a vital role in the occurrence, invasion, and metastasis of breast cancer (Ishibashi et al.1999, Aggarwal and Sloane 2014, Gomez-Auli et al.2016, Mitrovic et al.2017). In addition, cathepsin B may be served as potential marker for diagnosis and prognosis of breast cancer (Nouh et al.2011, Swisher et al.2015, Sun et al.2016). But no evidence supported targeting cathepsin B to be effective strategy for cancer therapy (Gondi and Rao 2013). In this study, Fmoc-GFLG, a cathepsin B responsive peptide, was used to link HSA and DOX and expected to give HSA-RB-DOX nanoparticles the characteristic of controlled release. Given that papain has the similar activity as cathepsin B, HSA-RB-DOX nanoparticles were expected to release more with the occurrence of papain. As shown in Figure 1(D), DOX was released more rapidly from HSA-RB-DOX nanoparticles with an accumulative release ratio of 88% in 80 h when papain was added, compared with 21% of no papain added. This result indicated HSA-RB-DOX nanoparticles were recognised and degraded by cathepsin B, and behaved controlled release characteristic at the tumour site.
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.
Related Knowledge Centers
- Cysteine Protease
- Exon
- Housekeeping Gene
- Amino Acid
- Lysosome
- Protein Family
- Papain-Like Protease
- Gene
- Chromosome 8
- Endoplasmic Reticulum