• 제목/요약/키워드: Cathepsin K

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A New Class of Potent Cathepsin K Inhibitors; OST-1857 Derivatives

  • Kim, N.C.;Han, T.D.;Hur, Y.;Hwang, H.J.;Shin, Y.A.;Lee, C.H.;Lee, B.Y.;Lee, J.W.;Bae, E.J.;Kim, M.K.;Yang, J.S.;Lim, J.I.;Son, M.H.;Kim, S.H.;Kim, W.B.
    • 대한약학회:학술대회논문집
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    • 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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    • pp.121.1-121.1
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    • 2001
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DNA Vaccines Encoding Toxoplasma gondii Cathepsin C 1 Induce Protection against Toxoplasmosis in Mice

  • Han, Yali;Zhou, Aihua;Lu, Gang;Zhao, Guanghui;Sha, Wenchao;Wang, Lin;Guo, Jingjing;Zhou, Jian;Zhou, Huaiyu;Cong, Hua;He, Shenyi
    • Parasites, Hosts and Diseases
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    • 제55권5호
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    • pp.505-512
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    • 2017
  • Toxoplasma gondii cathepsin C proteases (TgCPC1, 2, and 3) are important for the growth and survival of T. gondii. In the present study, B-cell and T-cell epitopes of TgCPC1 were predicted using DNAstar and the Immune Epitope Database. A TgCPC1 DNA vaccine was constructed, and its ability to induce protective immune responses against toxoplasmosis in BALB/c mice was evaluated in the presence or absence of the adjuvant ${\alpha}-GalCer$. As results, TgCPC1 DNA vaccine with or without adjuvant ${\alpha}-GalCer$ showed higher levels of IgG and IgG2a in the serum, as well as IL-2 and $IFN-{\gamma}$ in the spleen compared to controls (PBS, pEGFP-C1, and ${\alpha}-GalCer$). Upon challenge infection with tachyzoites of T. gondii (RH), $pCPC1/{\alpha}-GalCer$ immunized mice showed the longest survival among all the groups. Mice vaccinated with DNA vaccine without adjuvant (pCPC1) showed better protective immunity compared to other controls (PBS, pEGFP-C1, and ${\alpha}-GalCer$). These results indicate that a DNA vaccine encoding TgCPC1 is a potential vaccine candidate against toxoplasmosis.

Genetic aberrations on the short arm of chromosome 8 (8p) in tongue carcinomas

  • Murano, Akiyuki;Ono, Kanae;Koike, Hirofumi;Endo, Yosuke;Shimada, Ken;Kawasaki, Kenshi;Nomura, Hitomi;Shiiba, Masashi;Uzawa, Katsuhiro;Tanzawa, Hideki
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제38권2호
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    • pp.121-126
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    • 2012
  • Aberrations on the short arm of chromosome 8 (8p) are frequently observed in several human cancers. In this study, 20 squamous cell carcinoma (SCC) specimens from the tongue were examined in order to evaluate the role of 8p in SCC of the tongue. Microsatellite analysis using 14 markers demonstrated two commonly deleted regions (CDRs) on 8p. Reverse transcription-polymerase chain reaction (RT-PCR) revealed frequent down-regulation of the FEZ1 gene, mapped to 8p22, and frequent over-expression of the cathepsin B gene, mapped to 8p-21-22. These results suggested that genetic aberrations are involved in the development of SCC of the tongue. However, no significant relationship was observed to be established between the genetic alterations and clinicopathological features. Thus, further investigation is necessary in order to clarify the clinical role of 8p in carcinoma of the tongue.

Comparisons of orthodontic root resorption under heavy and jiggling reciprocating forces during experimental tooth movement in a rat model

  • Hikida, Takuji;Yamaguchi, Masaru;Shimizu, Mami;Kikuta, Jun;Yoshino, Tomokazu;Kasai, Kazutaka
    • 대한치과교정학회지
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    • 제46권4호
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    • pp.228-241
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    • 2016
  • Objective: Root mobility due to reciprocating movement of the tooth (jiggling) may exacerbate orthodontic root resorption (ORR). "Jiggling" describes mesiodistal or buccolingual movement of the roots of the teeth during orthodontic treatment. In the present study, buccolingual movement is described as "jiggling." We aimed to investigate the relationship between ORR and jiggling and to test for positive cell expression in odontoclasts in resorbed roots during experimental tooth movement (jiggling) in vivo. Methods: Male Wistar rats were divided into control, heavy force (HF), optimal force (OF), and jiggling force (JF) groups. The expression levels of cathepsin K, matrix metalloproteinase (MMP)-9 protein, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant 1 (CINC-1; an IL-8-related protein in rodents), receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL), and osteoprotegerin protein in the dental root were determined using immunohistochemistry. Results: On day 21, a greater number of root resorption lacunae, which contained multinucleated odontoclasts, were observed in the palatal roots of rats in the JF group than in rats from other groups. Furthermore, there was a significant increase in the numbers of cathepsin K-positive and MMP-9-positive odontoclasts in the JF group on day 21. Immunoreactivities for IL-6, CINC-1, and RANKL were stronger in resorbed roots exposed to jiggling than in the other groups on day 21. Negative reactivity was observed in the controls. Conclusions: These results suggest that jiggling may induce ORR via inflammatory cytokine production during orthodontic tooth movement, and that jiggling may be a risk factor for ORR.

mRNA Expression of Bax, Bcl-2, p53, Cathepsin B, Caspase-3 and Caspase-9 in the HepG2 Cell Line Following Induction by a Novel Monoclonal Ab Hep88 mAb: Cross-Talk for Paraptosis and Apoptosis

  • Mitupatum, Thantip;Aree, Kalaya;Kittisenachai, Suthathip;Roytrakul, Sittiruk;Puthong, Songchan;Kangsadalampai, Sasichai;Rojpibulstit, Panadda
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권2호
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    • pp.703-712
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    • 2016
  • Monoclonal antibodies with specific antigens have been widely used as targeted therapy for cancer. Hep88 mAb is a monoclonal antibody which shows specific binding with anti-cancer effects against the HepG2 cell line. However, its mechanisms of action are still not completely understood. We examined cell cycling and apoptosis by flow cytometry and mRNA expression of factors involved in apoptosis and paraptosis in Hep88 mAb-treated HepG2 cells by real-time PCR. The cell-cycle analysis demonstrated that growth-inhibitory activity was associated with G2/M cell cycle arrest. Hep88 mAb induced a significant increase in apoptotic cell populations in a dose- and time-dependent manner. The mRNA expression results also suggested that the process triggered by Hep88 mAb involved up-regulation of tumor suppressor p53, pro-apoptotic Bax, Cathepsin B, Caspase-3 and Caspase-9, with a decrease of anti-apoptotic Bcl-2 - thus confirming paraptosis and apoptosis programmed cell death. These findings represent new insights into the molecular mechanisms underlying the anti-cancer properties of Hep88 mAb in liver cancer cells.

Isolation and characterization of a cDNA encoding a mammalian cathepsin L-like cysteine proteinase from Acanthmoeba healui

  • Hong, Yeon-Chul;Hwang, Mi-Yul;Yun, Ho-Cheol;Yu, Hak-Sun;Kong, Hyun-Hee;Yong, Tai-Soon;Chung, Dong-Il
    • Parasites, Hosts and Diseases
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    • 제40권1호
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    • pp.17-24
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    • 2002
  • We have cloned a cDNA encoding a cysteine proteinase of the Acanthamoeba healui OC-3A strain isolated from the brain of a granulomatous amoebic encephalitis patient. A DNA probe for an A. healui cDNA library screening was amplified by PCR using degenerate oligonucleotide primers designed on the basis of conserved amino acids franking the active sites of cysteine and asparagine residues that are conserved in the eukaryotic cysteine proteinases. Cysteine proteinase gene of A. healui (AhCPI) was composed of 330 amino acids with signal sequence, a proposed pro-domain and a predicted active site made up of the catalytic residues, $Cys^{25},{\;}His^{159},{\;}and{\;}Asn^{175}$. Deduced amino acid sequence analysis indicates that AhCPI belong to ERFNIN subfamily of C 1 peptidases. By Northern blot analysis. no direct correlation was observed between AhCPI mRNA expression and virulence of Acanthamoeba, but the gene was expressed at higher level in amoebae isolated from soil than amoeba from clinical samples. These findings raise the possibility that AhCPI protein may play a role in protein metabolism and digestion of phagocytosed bacteria or host tissue debris rather than in invasion of amoebae into host tissue.

Expression of Yolk Processing Enzyme Genes in Fertilized Eggs from Artificially Matured Female Eel, Anguilla japonica

  • Oh, Hyeon Ji;Kim, Jung-Hyun;Mun, Seong Hee;Kim, Jin Hui;Kim, Dae-Jung;Kwon, Joon Yeong
    • 한국발생생물학회지:발생과생식
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    • 제22권3호
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    • pp.289-295
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    • 2018
  • Large quantity of eggs fail to be fertilized and many of fertilized eggs are unable to hatch in the eel, Anguilla japonica. Larvae of eel absorb egg yolk up to 8 days after hatching but the majority of hatched larvae die before they reach the stage of first feeding in this species. Genes of key enzymes for yolk processing (cathepsin B, D, L and lipoprotein lipase - abbreviated as ctsb, ctsd, ctsl and lpl, respectively) could be associated with egg quality. In this study, we investigated differences in the expression of these genes between floating eggs and sinking eggs, and also the relationship between the gene expressions of the enzymes and fertilization rates in the fertilized eggs obtained from artificially matured female eels. Expressions of yolk processing enzyme genes did not show significant difference between floating and sinking egg groups. Expression of ctsb decreased when fertilization rate was high. Expression of ctsd, ctsl and lpl, however, did not show any significant differences. These results suggest that ctsb expression could be an indicator of egg quality, and that some proteins prone to be digested by ctsb could be very important in the process of fertilization and normal cleavage in this species. Further study should identify these critical proteins to improve our understanding on the quality of fish eggs.

귀비탕(歸脾湯)이 파골세포 분화와 조골세포 활성에 미치는 영향 (The Effect of Guibi-tang Water Extract on Osteoclast Differentiation and Osteoblast Proliferation)

  • 최경희;유동열
    • 대한한방부인과학회지
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    • 제27권3호
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    • pp.12-27
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    • 2014
  • Objectives: This study was performed to evaluate the effect of Guibi-tang water extract (GB) on osteoporosis. Methods: We examined the effect of GB on osteoclast differentiation using murine pre-osteoclastic RAW 264.7 cells treated with receptor activator of nuclear factor kappa-B ligand (RANKL). The effect of GB on osteoclast was measured by counting TRAP (+) multinucleated cells and measuring TRAP activity. The mRNA expressions of osteoclastogenesis-related genes (Cathepsin K, MMP-9, TRAP, NFATc1, MITF, TNF-${\alpha}$, IL-6, COX-2) were measured by real-time PCR. We examined the effect of GB on osteoblast proliferation, ALP activity, bone matrix protein synthesis and collagen synthesis using murine calvarial cell. Results: GB decreased the number of TRAP (+) multinucleated cells and inhibited TRAP activity in RANKL-stimulated RAW 264.7 cell. GB decreased the expression of genes related osteoclastogenesis such as Cathepsin K, MMP-9, TRAP, NFATc1, MITF, COX-2 in RANKL-stimulated RAW 264.7 cell. But GB did not decrease the expression of iNOS and increased the expression of TNF-${\alpha}$, IL-6 in RANKL-stimulated RAW 264.7 cell. These genes (iNOS, TNF-${\alpha}$, IL-6) are thought to be related with the inflammatory bone destruction. GB increased cell proliferation of rat calvarial cell and also increased ALP activity in rat calvarial cell. GB did not increase bone matrix protein synthesis but increased collagen synthesis in rat calvarial cell. Conclusions: This study suggests that GB may be effective in treating osteoporosis by inhibiting osteoclast differentiation and its related gene expression and by increasing osteoblast proliferation.

원발성 위암 환자의 치료 전 PET/CT 스캔에서 FDG 섭취 정도와 임상병리학적 및 면역조직화학적 지표들과의 비교 (Comparison between FDG Uptake and Clinicopathologic and Immunohistochemical Parameters in Pre-operative PET/CT Scan of Primary Gastric Carcinoma)

  • 한은지;최우희;정용안;김기준;맹이소;손경명;정현석;손형선;정수교
    • Nuclear Medicine and Molecular Imaging
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    • 제43권1호
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    • pp.26-34
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    • 2009
  • 목적: 원발성 위암 환자의 PET/CT 스캔에서 FDG 섭취에 영향을 주는 임상병리학적 및 면역조직화학적 지표들이 있는지 알아보고자 하였다. 대상 및 방법: 본원에 내원하여 수술 전 FDG PET/CT 스캔을 시행한 89명의 위암환자들을 대상으로 하였다. PET/CT 영상에서 원발 종양의 SUVmax를 구한 후 침범 깊이(T기),종양 크기, 림프절전이, 종양 분화, Lauren의 분류, Ki-67 지수, p53, EGFR, Cathepsin D, c-erb-B2. COX-2의 발현과 같은 임상병리학적 및 면역조직화학적 지표들과의 상관 관계를 분석하였다. 결과: 89예의 위암 중 19예에서는 PET/CT 영상에서 인지 가능한 FDG 섭취가 없었는데, 이 19예 중 16예는 원발 종양의 침범 깊이가 점막하 이내에 국한된 경우였다. 위암의 FDG섭취 정도는 T기가 T2 이상일 때가 T1일 때보다 유의하게 높았고($5.8{\pm}3.1$ vs. $3.7{\pm}2.1$, p=0.002), 위암의 크기가 3 cm 이상일 경우가 3 cm 미만일 경우보다 유의하게 높았다($5.7{\pm}3.2$ vs. $3.7{\pm}2.0$, p=0.002) Lauren의 분류에 따른 장형 위암에서 장형이 아닐 때보다 높은 SUVmax를 보였다($5.4{\pm}2.8$ vs. $3.7{\pm}1.3$, p=0.003). 원발 종양의 SUVmax는 p53 양성인 경우가 음성인 경우보다 의미 있게 높았다($6.0{\pm}2.8$ vs. $4.4{\pm}3.0$, p=0.035). 그 외 림프절 전이 유무, 종양 분화, Ki-67 지수, EGFR, Cathepsin D, c-erb-B2 그리고 COX-2 같은 다른 지표들은 원발성 위암의 SUVmax와 의미 있는 상관 관계가 없었다. 결론: 원발성 위암의 침범 깊이(T기)는 FDG PET/CT 스캔에서의 위암 발견율에 영향을 주었다. 위암이 PET/CT스캔에서 인지 가능한 FDG 섭취를 보일 경우 T기, 종양의 크기, Lauren의 분류에 따른 조직형, 그리고 p53의 발현 정도는 원발성 위암의 FDG 섭취와 유의한 상관 관계가 있었다.