TY - JOUR
T1 - Inhibition of ADAMTS4 (aggrecanase-1) by tissue inhibitors of metalloproteinases (TIMP-1, 2, 3 and 4)
AU - Hashimoto, Gakuji
AU - Aoki, Takanori
AU - Nakamura, Hiroyuki
AU - Tanzawa, Kazuhiko
AU - Okada, Yasunori
PY - 2001/4/13
Y1 - 2001/4/13
N2 - 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.
AB - 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.
KW - A disintegrin and metalloproteinase
KW - A disintegrin and metalloproteinase with thrombospondin motifs 4
KW - Aggrecan degradation
KW - Aggrecanase
KW - Tissue inhibitor of metalloproteinases
UR - http://www.scopus.com/inward/record.url?scp=0035853456&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035853456&partnerID=8YFLogxK
U2 - 10.1016/S0014-5793(01)02323-7
DO - 10.1016/S0014-5793(01)02323-7
M3 - Article
C2 - 11311239
AN - SCOPUS:0035853456
SN - 0014-5793
VL - 494
SP - 192
EP - 195
JO - FEBS Letters
JF - FEBS Letters
IS - 3
ER -