Inhibition of ADAMTS4 (aggrecanase-1) by tissue inhibitors of metalloproteinases (TIMP-1, 2, 3 and 4)

被引：149

作者：

Hashimoto, G

Aoki, T

Nakamura, H

Tanzawa, K

Okada, Y

机构：

[1] Keio Univ, Sch Med, Dept Pathol, Shinjuku Ku, Tokyo 160016, Japan

[2] Sumitomo Pharmaceut Co Ltd, Div Res, Konohana Ku, Osaka 5540022, Japan

[3] Fuji Chem Ind Ltd, Dept Biopharmaceut, Toyama 9338511, Japan

[4] Sankyo Co Ltd, Biol Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

来源：

FEBS LETTERS | 2001年 / 494卷 / 03期

关键词：

tissue inhibitor of metalloproteinases; A disintegrin and metalloproteinase; A disintegrin and metalloproteinase with thrombospondin motifs 4; aggrecanase; aggrecan degradation;

D O I：

10.1016/S0014-5793(01)02323-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ADAMTS4 (aggrecanase-1) is considered to play. a key role in the degradation of aggrecan in arthritides, The inhibitory activity of tissue inhibitors of metalloproteinases (TIMPs) to ADAMTS4 was examined in an assay using aggrecan substrate. Among the four TIMPs, TIMP-3 inhibited the activity most efficiently with an IC50 value of 7.9 nM, which was at least 44-fold lower than that of TIMP-1 (350 nM) acid TIMP-2 (420 nM) and > 250-fold less than that of TIMP-4 (2 muM for 35% inhibition). These results suggest that TIMP-3 is a potent inhibitor against the aggrecanase activity of ADAMTS4 in vivo. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

收藏

页码：192 / 195

页数：4

相关论文

共 28 条

[1] The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3 [J].

Amour, A ;

Knight, CG ;

Webster, A ;

Slocombe, PM ;

Stephens, PE ;

Knäuper, V ;

Docherty, AJP ;

Murphy, G .

FEBS LETTERS, 2000, 473 (03) :275-279

[2] TNF-α converting enzyme (TACE) is inhibited by TIMP-3 [J].

Amour, A ;

Slocombe, PM ;

Webster, A ;

Butler, M ;

Knight, CG ;

Smith, BJ ;

Stephens, PE ;

Shelley, C ;

Hutton, M ;

Knäuper, V ;

Docherty, AJP ;

Murphy, G .

FEBS LETTERS, 1998, 435 (01) :39-44

[3] THE GENE STRUCTURE OF TISSUE INHIBITOR OF METALLOPROTEINASES (TIMP)-3 AND ITS INHIBITORY ACTIVITIES DEFINE THE DISTINCT TIMP GENE FAMILY [J].

APTE, SS ;

OLSEN, BR ;

MURPHY, G .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (24) :14313-14318

[4] Generation and characterization of aggrecanase - A soluble, cartilage-derived aggrecan-degrading activity [J].

Arner, EC ;

Pratta, MA ;

Trzaskos, JM ;

Decicco, CP ;

Tortorella, MD .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) :6594-6601

[5] A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells [J].

Black, RA ;

Rauch, CT ;

Kozlosky, CJ ;

Peschon, JJ ;

Slack, JL ;

Wolfson, MF ;

Castner, BJ ;

Stocking, KL ;

Reddy, P ;

Srinivasan, S ;

Nelson, N ;

Boiani, N ;

Schooley, KA ;

Gerhart, M ;

Davis, R ;

Fitzner, JN ;

Johnson, RS ;

Paxton, RJ ;

March, CJ ;

Cerretti, DP .

NATURE, 1997, 385 (6618) :729-733

[6] Role of the integrin-associated protein CD9 in binding between sperm ADAM 2 and the egg integrin α6β1:: Implications for murine fertilization [J].

Chen, MS ;

Tung, KSK ;

Coonrod, SA ;

Takahashi, Y ;

Bigler, D ;

Chang, A ;

Yamashita, Y ;

Kincade, PW ;

Herr, JC ;

White, JM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (21) :11830-11835

[7] Fertilization defects in sperm from mice lacking fertilinβ [J].

Cho, CH ;

Bunch, DO ;

Faure, JE ;

Goulding, EH ;

Eddy, EM ;

Primakoff, P ;

Myles, DG .

SCIENCE, 1998, 281 (5384) :1857-1859

[8] Shedding of syndecan-1 and-4 ectodomains is regulated by multiple signaling pathways and mediated by a TIMP-3-sensitive metalloproteinase [J].

Fitzgerald, ML ;

Wang, ZH ;

Park, PW ;

Murphy, G ;

Bernfield, M .

JOURNAL OF CELL BIOLOGY, 2000, 148 (04) :811-824

[9] Expression of ADAMTS homologues in articular cartilage [J].

Flannery, CR ;

Little, CB ;

Hughes, GE ;

Caterson, B .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 260 (02) :318-322

[10] Generation and novel distribution of matrix metalloproteinase-derived aggrecan fragments in porcine cartilage explants [J].

Fosang, AJ ;

Last, K ;

Stanton, H ;

Weeks, DB ;

Campbell, IK ;

Hardingham, TE ;

Hembry, RM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (42) :33027-33037