• Journal of Life Science
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• v.28 no.6
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• pp.753-763
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• 2018

Cysteine cathepsins are lysosomal enzymes that belong to the papain family and can induce the degradation of damaged proteins through the endo-lysosomal pathway. It is highly upregulated in many cancers by regulating gene amplification and transcriptional, translational, and post-transcriptional modifications. Cathepsin S is part of the cysteine cathepsin family. Many studies have demonstrated that cathepsin S not only plays a specific role in MHC class II antigen presentation but also plays a crucial role in cancers. Cathepsin S is more stable at a neutral pH compared to other cysteine cathepsins, which supports the importance of cathepsin S in disease microenvironments. Therefore, the dysregulation of cathepsin S has participated in a variety of pathological processes, including cancer, arthritis, and cardiovascular disease. Furthermore, a decrease or depletion in the expression of cathepsin S has been implicated in the processes of tumor growth, invasion, metastasis, and angiogenesis. Taken together, cathepsin S has been suggested as an attractive therapeutic target for cancer therapy. In this review, the known involvement of cathepsin S in diseases, particularly with respect to recent work indicating its role in cancer therapy, is examined. An overview of current literature on the inhibitors of cathepsin S as a therapeutic target for cancer is also provided.

• Food Science of Animal Resources
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• v.40 no.3
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• pp.415-425
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• 2020

It is believed that two main proteolytic systems are involved in the tenderization of meat: the cathepsins and the calpains. Many researchers consider the calpain system to be the major contributor to meat tenderness during post-mortem storage. However, the role and activity of cathepsins during post-mortem storage or low temperature meat processing is unclear, particularly for the tough meat cuts like brisket. Thus, the study was designed to investigate the effects of cold (refrigerated and frozen) storage and sous vide processing on the activities of cathepsin B, H, and L in beef brisket. There were no significant changes in pH and cathepsin H activity throughout the 18 d of storage at both temperatures. However, an increase in cathepsin B activity was observed during the first 4 d at both storage temperatures, but subsequently the activity remained unchanged. Cathepsins B and L were found to be more heat stable at sous vide temperatures (50℃ for 24 h, 55℃ for 5 h and at 60℃ and 70℃ for 1 h) compared to cathepsin H. Cathepsin B+L activity was found to increase after sous vide cooking at 50℃ for 1 h but decreased to about 47% relative to the uncooked control after 24 h of cooking. These results suggest that cathepsins B and L may contribute to the improved meat tenderness usually seen in sous vide cooked brisket meat.

• Microbiology and Biotechnology Letters
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• v.29 no.2
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• pp.84-89
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• 2001

Isolation and Characterization of Cathepsin B inhibitor Produced by Streptomyces luteogriseus KT-IO. Han, Kil~Hwan and Sang~Dal Kim*. Department of Applied Microbiology, Yeungnam Universit}/t Kyongsan 712749, Korea - The cathepsin B inhibitor produced by Streptomyces luteogriseus KT-IO was very stable in heat, acidic and alkaline conditions. The cathepsin B inhibitor was isolated from the extracted fraction of culture broth with butanol, methanol and chloroform subsequently, the inhibitor was purified with following several column chromatography sLlch as DEAE-Sephadex A-25, Sephadex G-15, silica gel 60, Sephadex LH-20, and preparative HPLC. The cathepsin B inhibitor showed positively to detective reaction of ninhydrine, 5% H2S04, iodine, but negatively to the reaction of Ehrlich's reagent, DNS, aniline. The molecular formular of cathepsin B inhibitor was elucidated by JR, lH and 13C-NMR, FAB mass and elemental analyzer. Consequently, it was identified as C4HlI04N6. The cathepsin B inhibitor had the mode of competitive inhibition with the reaction of cathepsin B.

• Microbiology and Biotechnology Letters
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• v.27 no.6
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• pp.458-465
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• 1999

Streptomyces luteogriseus KT-10 isolated from Korean farm soil produced a strong cathepsin B inhibitor. Optimal conditions for the cathepsin B inhibitor production by s. luteogriseus KT-10 were evaluated. The cathepsin B inhibitor was produced with maximal yield in the cultural condition of pH 7.0 and $25^{\circ}C$ for 4 days. Optimal medium for the cathepsin B inhibitor production was determined to be a medium containing 20g, peptone 3g, yeast extract 1g, K2HPO4 0.5g, MgSO4.7H2O 0.5g, NaNO3 0.5g, NaCl 0.5g per l. The cathepsin B inhibitor produced by S. luteogriseus KT-10 could also inhibit the other proteinases such as trypsin, papain, and cathepsin D.

• Journal of Fisheries and Marine Sciences Education
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• v.26 no.3
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• pp.543-552
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• 2014

Papain family중 하나인 cysteine protease는 근골격계 질환 치료를 위한target molecule로 인식 되어왔으며 Cathepsin B 는 단백질 분해의 초기과정에 관여하는 cysteine proteases 중 하나이다. 본 연구는 넙치의 cathepsin B 유전자의 발현 양상과 넙치 cathepsin B(PoCtB)의 클로닝, 발현 및 효소특성을 분석하였다. cDNA Library Screening을 이용하여 넙치의 cDNA를 클로닝하였다. 넙치의 동정된 cathepsin B 유전자는 993bp의 open reading frame과 330개의 아미노산으로 이루어져있다. Cathepsin B의 propeptide region 내에 GNFD motif와 occluding loop 가 존재함으로써 이것이 명백하게 cathepsin B group이라는 것을 보여주며, 계통 유전학적 분석 결과 다른 종의 cathepsin B에 비해 초창기에 분화되어 나온 것으로 사료된다. mature enzyme인 maPoCtB은 fusion protein인 glutathione S-transferase를 포함하는 pGEX-4T-1 vector에 삽입하여 E.coli 균주인 $DH5{\alpha}$ 내에 발현시켰다. 재조합 단백질인 PoCtB을 과발현 시킨 결과 53kDa의 분자량을 가진다. 넙치 cathepsin B 활성은 Z-Arg-Arg-AMC와 같은 fluorogenic 펩타이드 기질을 이용하여 측정되었고 적정 pH는 pH.7.5 이다.

• Microbiology and Biotechnology Letters
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• v.29 no.2
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• pp.90-95
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• 2001

Kinetic Analysis of Cathepsin B Inhibitor Using a Spectrophotometric Assay. Han, Kil-Hwan and SangDal Kim*. Department of Applied MicrobioJ0f5Yt Yeungnam UniversitYt Kyongsan 77 2-749, Korea - The KHS 10, C4Hl10~6 formula produced from Streptomyces luteogriseus KT-] 0 effectively inhibited a lysosomal cysteine proteinase, cathepsin B. It inhibited the enzyme activity of cathepsin B competitively when the N a-CBZ-Llysine p-nitrophenyl ester HC] (CLN) was used as a substrate. The inhibition const:mt (Ki) of KHS 1 0 for cathepsin B detennined by spectrophotometeric assay was 430 nM. The effective inhibition of cathepsin B was observed at $25^{\circ}C$ :md pH 6.0. The cathepsin B inhibitor, KHSlO needed a preincubation of cathepsin B with the inhibitor for over 5 min. The KHS 10 preserved over 80% inhibition activity even after heat-treatment at $100^{\circ}C$ for ] hr.

• Microbiology and Biotechnology Letters
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• v.23 no.5
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• pp.602-608
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• 1995

The aim of the present research program was to construct an optimum fermentation system and to characterize the properties of cathepsin B inhibitor from Streptomyces chromofuscus SMF28. Glucose and casitone were proved to be good carbon source and nitrogen source, respectively. The production of inhibitor was high at lower concentration than 10 mM of inorganic phosphate. The optimum temperature and pH for the production of inhibitor were 30$\circ$C and pH 7, respectively. The production of inhibitor was related to mycelial growth and was affected by medium composition. The inhibitor in culture filtrate of S. chromofuscus SMF28 was purified by butanol extraction, silica gel chromatography, Amberlite IRC-50 (H$^{+}$ form) chromatography, preparative TLC, and preparative HPLC. From amino acid analysis and UV, IR, $^{1}$H-NMR spectroscopic analysis, the inhibitor was identified as a peptide containing valine and phenylalanine derivative.

• YAKHAK HOEJI
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• v.39 no.3
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• pp.306-313
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• 1995

The aim of the present study was to produce low molecular weight cathepsin B inhibitor. A strain of Streptomyces aburabiensis isolated from soil in Korea was selected and the optimum condition for the production of the inhibitor was evaluated. Glucose and soytone were selected as best carbon and nitrogen sources, respectively. From the kinetic analysis in batch fermentation, it was found that the specific cathepsin B inhibitor production rate (q$_{p}$) was linearly related to specific growh rate ($\mu$). The inhibitor in culture filtrate was purified by adsorption on activated charcoal, butanot extraction, silica gel chromatography, ion exchange chromatography using Dowex-1 (Cl form) and Amberlite IRC-50 (H$^{+}$ form), and preparative TLC. From the UV, IR, Mass spectroscopy and $^{1}$H-NMR, the inhibitor was thought to be a new inhibitor of which molecular weight was 199.

• Journal of dental hygiene science
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• v.6 no.1
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• pp.1-9
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• 2006

Cathepsin K (cat K) is the major cysteine protease expressed in osteoclasts and was thought to play a key role in matrix degradation during bone resorption. It was shown that the intracellular maturation of cat K was prevented by the cAMP antagonist, Rp-cAMP, and the protein kinase A (PKA) inhibitors of KT5720 and H89. In contrast, forskolin, a adenylate cyclase agonist, rather induced Cat K processing and maturation in osteoclasts. Furthermore, to determine whether cat K processing and maturation signaling involves protein kinase C (PKC), mouse total bone cells were treated with calphostin C, a specific inhibitor of PKC, however, no effect was observed, indicating that calphostin C did not affect to osteoclast-mediated cat K processing and maturation. Thus, it is indicated that the cAMP-PKA signaling pathway regulates cat K maturation in osteoclasts. Since secreted proenzymes have the potential to reenter the cell via M6P receptor, to prevent this possibility, it was tested cAMP antagonist Rp-cAMP and the PKA inhibitors KT5720 and H89 in the absence or presence of M6P. Inhibition of cat K processing by Rp-cAMP, KT5720, or H89 was observed in a dose-dependent manner. Furthermore, the addition of M6P resulted in enhanced potency of Rp-cAMP, KT5720 and H89. These dose-dependently inhibited in vitro bone resorption with a potency similar to that observed for inhibition of cat K processing.

• The Korean Journal of Malacology
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• v.29 no.2
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• pp.155-161
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• 2013

Cathepsins are lysosomal/cysteine proteases belong to papain family (C1 family) that is involved in intracellular protein degradation, antigen processing, hormone maturation, and immune responses. In this study, member of cathepsin family was identified from Manila clam (Mc-Cathepsin D) and investigated the immune response against brown ring disease (BRD) causing Vibrio tapetis challenge. The identified Mc-Cathepsin D gene encodes characteristic features typical for the cathepsin family including eukaryotic and viral aspartyl protease signature domain and two highly conserved active sites ($^{84}VVFDTGSSNLWV^{95}$ and $^{270}IADTGTSLLAG^{281}$). Moreover, MC-Cathepsin D shows higher identity values (-50-70%) and conserved amino acids with known cathepsin D members. Transcriptional results (by quantitative real-time RT-PCR) showed that Mc-Cathepsin D was expressed at higher levels in gills and hemocytes than mantle, adductor muscle, foot, and siphon. After the V. tapetis challenge under laboratory conditions, Mc-Cathepsin D mRNA was up-regulated in gills and hemocytes. Present study indicates that Mc-Cathepsin D is constitutively expressed in different tissues and potentially inducible when infecting BRD by V. tapetis. It is further suggesting that Mc-Cathepsin D may be involved in multiple role including immune response reactions against BRD.