The degradation of tissue inhibitor of metalloproteinase (TIMP)-free matrix metalloproteinase (MMP)-2 to proteolytically inactive fragments by plasmin was inhibited in equimolar mixtures of purified TIMP-2 and TIMP-free MMP-2 and was not observed in purified MMP-2-TIMP-2 complexes. Divalent cation chelators EDTA and sodium Alendronate did not inhibit plasmin degradation of TIMP-free MMP-2 but reversed the ability of TIMP-2 to protect MMP-2 from degradation by plasmin. Our data confirm a role for plasmin in the clearance of TIMP-free MMP-2, identify a pivotal role for TIMP-2 in regulating MMP-2 longevity in plasmin-containing environments, and highlight a novel therapeutic use for chelators of divalent cations, including the bisphosphonate.Alendronate, in the reversal of TIMP-2 protection of MMP-2 from degradation by plasmin. We propose that these observations are relevant to pathologies that are dependent upon plasmin and MMP-2 activity (e.g., tumor invasion and metastasis).

Tissue inhibitor of metalloproteinase-2 protection of matrix metalloproteinase-2 from degradation by plasmin is reversed by divalent cation chelator EDTA and the bisphosphonate alendronate

Farina AR;TETI, ANNA MARIA;MACKAY, ANDREW REAY
1998-01-01

Abstract

The degradation of tissue inhibitor of metalloproteinase (TIMP)-free matrix metalloproteinase (MMP)-2 to proteolytically inactive fragments by plasmin was inhibited in equimolar mixtures of purified TIMP-2 and TIMP-free MMP-2 and was not observed in purified MMP-2-TIMP-2 complexes. Divalent cation chelators EDTA and sodium Alendronate did not inhibit plasmin degradation of TIMP-free MMP-2 but reversed the ability of TIMP-2 to protect MMP-2 from degradation by plasmin. Our data confirm a role for plasmin in the clearance of TIMP-free MMP-2, identify a pivotal role for TIMP-2 in regulating MMP-2 longevity in plasmin-containing environments, and highlight a novel therapeutic use for chelators of divalent cations, including the bisphosphonate.Alendronate, in the reversal of TIMP-2 protection of MMP-2 from degradation by plasmin. We propose that these observations are relevant to pathologies that are dependent upon plasmin and MMP-2 activity (e.g., tumor invasion and metastasis).
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11697/23281
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 24
social impact