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Superoxide regulation of endothelin-converting enzyme
S López-Ongil1, V Senchak, M Saura
1Divisions of Cardiology and Nephrology, the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
The Journal of Biological Chemistry
|June 2, 2000
Summary
Excess superoxide, a type of reactive oxygen species (ROS), inhibits endothelin-converting enzyme (ECE) activity by removing zinc. This finding reveals a protective vascular mechanism against excessive ROS, impacting endothelin-1 synthesis.
Area of Science:
- Cardiovascular Biology
- Oxidative Stress Research
- Enzymology
Background:
- Reactive oxygen species (ROS) are crucial signaling molecules in the cardiovascular system, regulating cell proliferation and migration.
- However, elevated ROS levels can cause cellular damage and impair endothelial cell function.
Purpose of the Study:
- To investigate endogenous mechanisms that protect the vasculature from excessive reactive oxygen species (ROS).
- To determine the specific effects of different ROS, including superoxide, hydrogen peroxide, and nitric oxide, on endothelin-converting enzyme (ECE) activity.
Main Methods:
- Assessing the impact of superoxide, hydrogen peroxide, and nitric oxide on endothelin-converting enzyme (ECE) activity in vitro.
- Investigating the mechanism of superoxide-induced ECE inhibition, specifically focusing on zinc interaction.
- Evaluating the effect of exogenous zinc supplementation on restoring ECE activity.
Main Results:
- Superoxide was found to inhibit endothelin-converting enzyme (ECE) activity and reduce endothelin-1 synthesis.
- Hydrogen peroxide and nitric oxide did not exhibit inhibitory effects on ECE activity.
- Superoxide inhibits ECE by displacing zinc ions from the enzyme; adding external zinc restored enzymatic function.
Conclusions:
- Superoxide acts as a regulator of endothelin-converting enzyme (ECE) activity, thereby influencing endothelin-1 synthesis.
- The mechanism of inhibition involves zinc ejection, suggesting a broader role for superoxide in regulating zinc metalloproteinases within blood vessels.
- This study uncovers a novel endogenous protective mechanism in the vasculature against oxidative stress.