• 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 and Biotechnology
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• v.18 no.1
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• pp.84-88
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• 2009

Cathepsin S is a cysteine protease that affects extracellular matrix remodeling. Recently, several studies have reported that cathepsin S is involved in obesity. Both mouse and human adipose cells produce this enzyme in the early phase of adipocyte differentiation, where it degrades fibronectin. Cathepsin S gene expression is elevated in the adipose tissue of obese mice as compared to that of lean mice. Paecilomyces tenuipes water extracts (PTW) are shown to have an inhibitory effect on cathepsin S activity. In this study, Z-Val-Val-Arg-MCA was used as a cathepsin S-specific substrate in order to examine inhibitory effect of PTW. Supplementing 3T3-L1 cell media with PTW clearly reduced lipid droplet accumulation and cathepsin S-induced adipogenesis. Furthermore, PTW decreased weight gain, subcutaneous adipose tissue growth, the level of serum triglyceride, and total cholesterol in mice fed a high-fat diet. These data suggest that PTW work against adipose cathepsin S and presumably contribute to anti-obese activities.

• Advances in pediatric surgery
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• v.5 no.1
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• pp.39-44
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• 1999

Diagnosing Hirschprung's disease is one of the clinical challenges of this disorder. In the stomach and the intestines, Cathepsin D was readily detected in cytoplasm of the rat gastric and in intestinal ganglion cells of the autonomic nervous system. The objectives of the present study were to examine cathepsin D expression in ganglion cells of the submucosal and myenteric plexuses of the intestine of children and to determine the utility of immunohistochemical staining of cathepsin D for detection of immature ganglion cells. Paraffin blocks of 35 intestinal segments were reviewed for immunohistochemical staining with polyclonal antibody to cathepsin D and hematoxylineosin stainings from the compatible specimens. There were 9 aganglionic segments and 9 ganglionic segments of neonates with Hirschsprung's disease, 8 intestinal segments with non-Hirschsprung's disease in neonates and 9 intestinal segments with non-Hirschsprung's disease infants over the age of 10 months. All ganglion cells showed intense granular cytoplasmic reactivity for cathepsin D regardless of maturity and all aganglionic segments had no expression for cathepsin D in the submucosal and myenteric plexuses of the intestine. However, histiocytes within the laminar propria and submucosa stained positively for cathepsin D. In conclusion, intestinal ganglion cells in children have reactivity for cathepsin D, threrfore immunohistochemical staining for cathepsin D can be used for identification of ganglion cells in neonates.

• 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 Acupuncture Research
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• v.20 no.3
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• pp.104-116
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• 2003

목적 : 시스테인 단백분해 효소인 cathepsin는 인간과 생쥐의 항원제시세포에서 II형 주적합항원 불변사슬(MHC class II invariant chain)의 분해에 관여한다. 본 연구는 녹용 약침액이 류마티스 관절염 생쥐 모델의 골조직(연골과 활액) 유래 cathepsin 활성에 미치는 영향을 검정하였다. 방법 : 관절염 동물모델은 BALb/c계 생쥐를 생후 3일에 흉선 적출(3d-Tx)을 하여 만들었다. 동물모델의 골조직, 임파절세포, 비장 등을 녹용처치군과 대조군으로 나누어 cathepsin의 활성도 및 자가항원 특이(C-II-specific) T-세포의 활성도를 비교 분석하였다. 결과 : 각 장기에서 cathepsin S의 활성은 녹용약침 처치군에서 농도 의존적으로 유의성 있게 억제되었고, T-세포 특이 자가항원반응은 녹용약침 처치군의 임파절 세포에서 유의성있게 억제되었다. 그리고 T-세포 특이 자가항원 반응의 불활성화에는 녹용 10~20ug/ml의 용량으로 충분하였다. 결론 : 이러한 실험결과는 녹용 약침액이 cathepsin S를 선택적으로 억제시켜 류마티스 관절염과 같은 자가면역 질환에 유효한 치료약물로 사용될 수 있음을 시사한다.

• 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.

• YAKHAK HOEJI
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• v.39 no.3
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• pp.297-305
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• 1995

The aim of the present study was to develop strains of actinomycetes producing low molecular weight cathepsin B inhibitor. Among 700 isolates from soil samples, a strain of Streptomyces sp. SMF30 producing cathepsin B inhibitor showing specificity and heat stability was selected by an economical and effective screening method. 50 units characteristics for major cluster analysis and 34 units characteristics for minor cluster were tested and the data were analyzed numerically using the TAXON program. The Isolate SMF30 was identified as a strain of Streptomyces aburabiensis

• Microbiology and Biotechnology Letters
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• v.29 no.1
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• pp.25-30
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• 2001

A strain of Actinomycetes producing cathepis B inhibitor was isolated from soil and identified as Streptomyces misakiensis. The product of S. misakiensis inhibited effectively cathepsis B proteinases as well as trypsin and papain. The cathepsin B inhibitor were largely produced with incubation for 4 days. The S. misakiensis was the most growth with incubation for 5 days. The cathepsin B inhibitor was isolated from the extraction of both with ethanol, ethanol and chlorofrom, and following several column chromatography such as sephadex G-15, silica gel 60 and sephadex LH-20 chromatography. The moleculer weight of purfied inhibitor was 138 dalton.

• 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.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.51-54
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• 1990

Human leukocyte cathepsin-Gs are active participant in the active phase of inflammations like rheumatoid arthritis, emphysema and glomerular injury. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for treatment of these inflammatory diseases. Mechanism of action of NSAIDs for treatment of inflammatory diseases, especially like rheumatoid arthritis, are known as the inhibitors of prostaglandin synthesis. Inhibitions of the activities of human leukocyte cathepsin-Gs by non-steroidal anti-inflammatory drugs, however, were not same as the known pharmacological effects (inhibition of cyclooxygenase) of these drugs. Among them, especially, sulindac, salicylate, phenylbutazone, oxyphenbutazone, and salicyluric acid inhibited human leukocyte cathepsin-Gs effectively. $IC_{50}s$ of each drug were 4.3mM, 14.3mM, 6.5mM, 11mM and 15mM respectively. The drugs which have same chemical structure and same degree of inhibition effect on cyclooxygenase showed different degree or no effect on inhibition of cathepsin G. These inhibition effect might be, beside of inhibition of cyclooxygenase in the prostaglandin synthesis pathway, another benefitial antiinflammatory effect of NSAIDs by direct protection against tissue destruction in inflammatory diseases.