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

FEBS Letters

Aoki, Takanori¹  Nakamura, Hiroyuki³  Tanzawa, Kazuhiko²  Okada, Yasunori³  Hashimoto, Gakuji³ 

[1] Biopharmaceutical Department, Fuji Chemical Industries, Ltd., 530 Chokeiji, Takaoka, Toyama 933-8511, Japan;Biological Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan;Department of Pathology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-0016, Japan

关键词: Tissue inhibitor of metalloproteinases;    A disintegrin and metalloproteinase;    A disintegrin and metalloproteinase with thrombospondin motifs 4;    Aggrecanase;    Aggrecan degradation;    ADAMTS;    a disintegrin and metalloproteinase with thrombospondin motifs;    CaPPS;    calcium pentosan polysulfate;    CBB;    Coomassie brilliant blue R-250;    MMP;    matrix metalloproteinase;    SDS–PAGE;    sodium dodecyl sulfate–polyacrylamide gel electrophoresis;   

DOI  :  10.1016/S0014-5793(01)02323-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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) and TIMP-2 (420 nM) and >250-fold less than that of TIMP-4 (2 μM for 35% inhibition). These results suggest that TIMP-3 is a potent inhibitor against the aggrecanase activity of ADAMTS4 in vivo.

【 授权许可】

Unknown