Mechanism of Heparin Acceleration of Tissue Inhibitor of Metalloproteases-1 (TIMP-1) Degradation by the Human Neutrophil Elastase
2011

Heparin Accelerates TIMP-1 Hydrolysis by Human Neutrophil Elastase

publication Evidence: moderate

Author Information

Author(s): Nunes Gabriel L. C., Simões Alyne, Dyszy Fábio H., Shida Claudio S., Juliano Maria A., Juliano Luiz, Gesteira Tarsis F., Nader Helena B., Murphy Gillian, Chaffotte Alain F., Goldberg Michel E., Tersariol Ivarne L. S., Almeida Paulo C.

Primary Institution: Centro Interdisciplinar de Investigação Bioquímica, Universidade de Mogi das Cruzes, Mogi das Cruzes, Brazil

Hypothesis

Heparin regulates the activity of human neutrophil elastase (HNE) on Tissue Inhibitor of Metalloproteases-1 (TIMP-1).

Conclusion

Heparin increases the rate of TIMP-1 hydrolysis by HNE by 2.5-fold.

Supporting Evidence

  • Heparin accelerates TIMP-1 hydrolysis by HNE by 2.5-fold.
  • The presence of heparin alters the kinetic parameters of HNE, increasing k_cat and decreasing K_M.
  • Heparin shifts the pH activity profile of HNE to allow activity at alkaline pH.

Takeaway

Heparin helps a protein called neutrophil elastase break down another protein called TIMP-1 faster, which is important for how our body responds to inflammation.

Methodology

The study used recombinant TIMP-1 and FRET-peptides to assess the effect of heparin on HNE activity through various kinetic assays.

Digital Object Identifier (DOI)

10.1371/journal.pone.0021525

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