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Inhibition of inflammatory proteinase, medullasin, by alpha 2-macroglobulin and ovomacroglobulin
1Dept. of Biophysics and Biochemistry, Faculty of Science, Univ. of Tokyo, Japan.
Abstract:
The in vitro activity of inflammatory proteinase, medullasin, was stoichiometrically inhibited by a serum proteinase inhibitor, alpha 2-macroglobulin, and its homolog, chicken ovomacroglobulin. The two inhibitors were cleaved by medullasin only in the bait region. The effectiveness of alpha 2-macroglobulin to inhibit medullasin in competition with alpha -1-proteinase inhibitor was measured under a simulated in vivo condition and an estimation was made that about 60-70% medullasin is inhibited by alpha-1-inhibitor and 30-40% by alpha 2-macroglobulin.
Insights
Serum proteinase inhibitors, alpha 2-macroglobulin and chicken ovomacroglobulin, stoichiometrically inhibit medullasin. Alpha-1-proteinase inhibitor accounts for most medullasin inhibition in vivo.
Area of Science:
- Biochemistry
- Enzymology
- Immunology
Background:
- Medullasin is an inflammatory proteinase.
- Alpha 2-macroglobulin (α2M) and chicken ovomacroglobulin are serum proteinase inhibitors.
- Alpha-1-proteinase inhibitor (α1PI) is another key serum proteinase inhibitor.
Purpose of the Study:
- To investigate the in vitro inhibition of medullasin by α2M and chicken ovomacroglobulin.
- To determine the relative contributions of α2M and α1PI in inhibiting medullasin under simulated in vivo conditions.
Main Methods:
- Stoichiometric inhibition assays were performed.
- Cleavage sites within the inhibitors were identified.
- Competitive inhibition experiments were conducted under simulated in vivo conditions.
Main Results:
- Medullasin was stoichiometrically inhibited by both α2M and chicken ovomacroglobulin.
- Cleavage of both inhibitors by medullasin occurred exclusively in their respective bait regions.
- Under simulated in vivo conditions, α1PI inhibited 60-70% of medullasin activity, while α2M inhibited 30-40%.
Conclusions:
- Alpha 2-macroglobulin and chicken ovomacroglobulin effectively inhibit medullasin in vitro.
- Alpha-1-proteinase inhibitor plays a dominant role in the in vivo inhibition of medullasin compared to alpha 2-macroglobulin.