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Aggrecanase-1 (ADAMTS-4) interacts with alpha1-antitrypsin
Koji Yoshida1, Yasuyuki Suzuki, Akio Saito
1Department of Biochemistry, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan. kojiy@med.kindai.ac.jp
Biochimica Et Biophysica Acta
|August 16, 2005
Summary
Alpha1-antitrypsin binds to aggrecanase-1 in vivo, a key enzyme in cartilage degradation associated with arthritis. However, this interaction does not affect their individual functions, suggesting an unclear physiological role.
Area of Science:
- Biochemistry
- Molecular Biology
- Rheumatology
Background:
- Degradative articular diseases like rheumatoid arthritis and osteoarthritis involve extracellular matrix loss and joint cartilage destruction.
- Aggrecan proteolysis is an early event in matrix breakdown, with aggrecanase-1 (ADAMTS-4) playing a critical role in cartilage aggrecan abrasion.
Purpose of the Study:
- To identify endogenous inhibitors of aggrecanase-1.
- To investigate the interaction between aggrecanase-1 and alpha1-antitrypsin.
Main Methods:
- Yeast two-hybrid screen using the catalytic domain of human aggrecanase-1.
- Expression of recombinant aggrecanase-1 and alpha1-antitrypsin in mammalian cells.
- Co-immunoprecipitation experiments to assess in vivo association.
Main Results:
- Alpha1-antitrypsin was identified as a binding partner for aggrecanase-1 via yeast two-hybrid screening.
- Co-immunoprecipitation confirmed in vivo association between full-length aggrecanase-1 and alpha1-antitrypsin.
- Aggrecanase-1 did not inhibit alpha1-antitrypsin's activity against elastase, nor did alpha1-antitrypsin affect aggrecanase-1's proteolytic activity.
Conclusions:
- Aggrecanase-1 and alpha1-antitrypsin interact and bind in vivo.
- The physiological significance of the aggrecanase-1 and alpha1-antitrypsin interaction remains to be elucidated.