Open AccessThioredoxin alters the matrix metalloproteinase/tissue inhibitors of metalloproteinase balance and stimulates human SK‐N‐SH neuroblastoma cell invasion
Author(s) -
Farina Antonietta R.,
Tacconelli Antonella,
Cappabianca Lucia,
Masciulli MariaPaola,
Holmgren Arne,
Beckett Geoffery J.,
Gulino Alberto,
Mackay Andrew R.
Publication year - 2001
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1033.2001.01892.x
Subject(s) - thioredoxin reductase , thioredoxin , matrix metalloproteinase , metalloproteinase , chemistry , tissue inhibitor of metalloproteinase , extracellular matrix , biochemistry , cancer research , microbiology and biotechnology , enzyme , biology
Thioredoxin (Trx) inhibited tissue inhibitor of metalloproteinase (TIMP)‐1 and TIMP‐2 activity with an approximate IC 50 of 0.3 µ m , matrix metalloproteinase (MMP)‐2 activity with an approximate IC 50 of 2 µ m but did not inhibit MMP‐9 activity. This differential capacity of Trx to inhibit TIMP and MMP activity resulted in the promotion of MMP‐2 and MMP‐9 activity in the presence of molar TIMP excess. Inhibition of TIMP and MMP‐2 activity by Trx was dependent upon thioredoxin reductase (TrxR), was abolished by Trx catalytic site mutation and did not result from TIMP or MMP‐2 degradation. HepG2 hepatocellular carcinoma cells induced to secrete Trx inhibited TIMP activity in the presence of TrxR. SK‐N‐SH neuroblastoma cells secreted TrxR, which inhibited TIMP and MMP‐2 activity in the presence of Trx. Trx stimulated SK‐N‐SH invasive capacity in vitro in the absence of exogenous TrxR. This study therefore identifies a novel extracellular role for the thioredoxin/thioredoxin reductase redox system in the differential inhibition of TIMP and MMP activity and provides a novel mechanism for altering the TIMP/MMP balance that is of potential relevance to tumor invasion.