TAILIEUCHUNG - Báo cáo khoa học: Inhibitory properties of cystatin F and its localization in U937 promonocyte cells

Cystatin F is a recently discovered type II cystatin expressed almost exclu-sively in immune cells. It is present intracellularly in lysosome-like vesicles, which suggests a potential role in regulating papain-like cathepsins involved in antigen presentation. Therefore, interactions of cystatin F with several of its potential targets, cathepsins F, K, V, S, H, X and C, were studied in vitro. Cystatin F tightly inhibited cathepsins F, K and V with Ki values ranging from nmto nm, whereas cathepsins S and H were inhib-ited with 100-fold lower affinities (Ki 30 nm). The exopeptidases, cathep-sins C and X were not inhibited by cystatin F | ềFEBS Journal Inhibitory properties of cystatin F and its localization in U937 promonocyte cells TomaZ Langerholc1 Valentina Zavasnik-Bergant1 Boris Turk1 Vito Turk1 Magnus Abrahamson2 and Janko Kos3 1 Department of Biochemistry and Molecular Biology Jozef Stefan Institute Ljubljana Slovenia 2 Department of ClinicalChemistry Institute of Laboratory Medicine University of Lund Sweden 3 Faculty of Pharmacy Department of PharmaceuticalBiology University of Ljubljana Slovenia Keywords cathepsin cysteine protease inhibition cystatin antigen presentation Correspondence T. Langerholc Department of Biochemistry and Molecular Biology Jozef Stefan Institute Ljubljana Slovenia Fax 386 14773984 Tel 386 14773573 E-mail Received 9 November 2004 revised 31 January 2005 accepted 2 February 2005 doi Cystatin F is a recently discovered type II cystatin expressed almost exclusively in immune cells. It is present intracellularly in lysosome-like vesicles which suggests a potential role in regulating papain-like cathepsins involved in antigen presentation. Therefore interactions of cystatin F with several of its potential targets cathepsins F K V S H X and C were studied in vitro. Cystatin F tightly inhibited cathepsins F K and V with Ki values ranging from nM to nM whereas cathepsins S and H were inhibited with 100-fold lower affinities Ki w 30 nM . The exopeptidases cathepsins C and X were not inhibited by cystatin F. In order to investigate the biological significance of the inhibition data the intracellular localization of cystatin F and its potential targets cathepsins B H L S C and K were studied by confocal microscopy in U937 promonocyte cells. Although vesicular staining was observed for all the enzymes only cathepsins H and X were found to be colocalized with the inhibitor. This suggests that cysta-tin F in U937 cells may function as a regulatory inhibitor of proteolytic activity of cathepsin H or more likely .

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