Related Experiment Videos
Myocardial matrix metalloproteinase(s): localization and activation
S C Tyagi1, A Ratajska, K T Weber
1Department of Internal Medicine, University of Missouri-Columbia 65212.
Molecular and Cellular Biochemistry
|September 8, 1993
Summary
Matrix metalloproteinases (MMPs) activate in the heart via serine proteases or oxidized glutathione (GSSG), with synergistic effects observed. These MMPs are localized within the myocardium, suggesting a role in cardiac remodeling and disease.
Area of Science:
- Biochemistry
- Cardiovascular Biology
- Enzymology
Background:
- Matrix metalloproteinases (MMPs) and neutrophil elastase (NE) are implicated in collagen degradation.
- Limited knowledge exists regarding MMP activation and localization within the heart.
Purpose of the Study:
- To investigate the mechanisms of proMMP activation in adult rat myocardium.
- To determine the localization of proMMPs/MMPs in cardiac tissue.
Main Methods:
- Extraction of MMPs from adult rat myocardium.
- Incubation of extracts with serine proteases (trypsin, NE) and oxidized glutathione (GSSG).
- Analysis using immunoblot, zymography, reverse zymography, and indirect immunofluorescence.
Main Results:
- ProMMP activation was time-dependent when incubated with serine proteases or GSSG.
- Active MMPs were identified at 52 kDa.
- Serine protease and GSSG synergistically increased proMMP activation rates up to 30-fold.
- Tissue inhibitors of metalloproteinases were identified.
- ProMMPs/MMPs were localized to the endocardium and interstitial spaces of the myocardium.
Conclusions:
- MMP activation in the heart occurs through distinct mechanisms involving serine proteases and oxidizing reagents.
- The presence of serine proteases or GSSG significantly enhances MMP activation.
- Endogenous inhibitors may regulate MMP activity.
- Further research is needed to establish the role of MMPs in cardiac remodeling and disease states.