Thioredoxin alters the matrix metalloproteinase/tissue inhibitors of metalloproteinase balance and stimulates human SK-N-SH neuroblastoma cell invasion

Antonietta R. Farina, Antonella Tacconelli, Lucia Cappabianca, Maria Paola Masciulli, Arne Holmgren, Geoffery J. Beckett, Alberto Gulino, Andrew R. Mackay

Research output: Contribution to journalArticle

Abstract

Thioredoxin (Trx) inhibited tissue inhibitor of metallopro-teinase (TIMP)-1 and TIMP-2 activity with an approximate IC 50 of 0.3 μm, matrix metalloproteinase (MMP)-2 activity with an approximate IC 50 of 2 μm 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.

Original languageEnglish
Pages (from-to)405-413
Number of pages9
JournalEuropean Journal of Biochemistry
Volume268
Issue number2
DOIs
Publication statusPublished - 2001

Keywords

  • Invasion
  • Metalloproteinase
  • Thioredoxin
  • Thioredoxin reductase
  • Tissue inhibitor of metallo-proteinases

ASJC Scopus subject areas

  • Biochemistry

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