Type

Journal Article

Authors

N G McElvaney
R L Levine
S J O'Neill
A T Mulgrew
C M Greene
G J Lowe
C C Taggart

Subjects

Biochemistry

Topics
humans metabolism proteins catalytic domain recombinant proteins female protein binding case control studies cathepsin s chemistry enzymology slpi protein human male epithelium middle aged cathepsins threonine cysteine endopeptidases pharmacology emphysema cathepsin l ctsl1 protein human time factors proteinase inhibitory proteins secretory alpha 1 antitrypsin blotting western electrophoresis polyacrylamide gel chromatography high pressure liquid animals binding sites cathepsin b bronchoalveolar lavage lung secretory leukocyte peptidase inhibitor enzyme activation tyrosine enzyme inhibitors

Cathepsin B, L, and S cleave and inactivate secretory leucoprotease inhibitor. (2001)

Abstract A number of serine proteases, matrix metalloproteases, and cysteine proteases were evaluated for their ability to cleave and inactivate the antiprotease, secretory leucoprotease inhibitor (SLPI). None of the serine proteases or the matrix metalloproteases examined cleaved the SLPI protein. However, incubation with cathepsins B, L, and S resulted in the cleavage and inactivation of SLPI. All three cathepsins initially cleaved SLPI between residues Thr(67) and Tyr(68). The proteolytic cleavage of SLPI by all three cathepsins resulted in the loss of the active site of SLPI and the inactivation of SLPI anti-neutrophil elastase capacity. Cleavage and inactivation were catalytic with respect to the cathepsins, so that the majority of a 400-fold excess of SLPI was inactivated within 15 min by cathepsins L and S. Analysis of epithelial lining fluid samples from individuals with emphysema indicated the presence of cleaved SLPI in these samples whereas only intact SLPI was observed in control epithelial lining fluid samples. Active cathepsin L was shown to be present in emphysema epithelial lining fluid and inhibition of this protease prevented the cleavage of recombinant SLPI added to emphysema epithelial lining fluid. Taken together with previous data that demonstrates that cathepsin L inactivates alpha(1)-antitrypsin, these findings indicate the involvement of cathepsins in the diminution of the lung antiprotease screen possibly leading to lung destruction in emphysema.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

N G McElvaney, R L Levine, S J O'Neill, A T Mulgrew, C M Greene, G J Lowe, C C Taggart

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
3
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
4
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54