Superoxide Regulation of Endothelin-converting Enzyme*
- Susana López-Ongil‡,
- Veronica Senchak§,
- Marta Saura‡,
- Carlos Zaragoza,
- Michael Ames¶,
- Barbara Ballermann§,
- Manuel Rodrı́guez-Puyol‡,
- Diego Rodrı́guez-Puyol‡ and
- Charles J. Lowenstein‖**
- From the Divisions of ‖Cardiology and §Nephrology, the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, the ‡Department of Physiology, Research Unit and IRSIN, Alcala de Henares University, 28871 Madrid, Spain, and the ¶Nuclear Reactor Laboratory, Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02138
Abstract
Reactive oxygen species (ROS) act as signaling molecules in the cardiovascular system, regulating cellular proliferation and migration. However, an excess of ROS can damage cells and alter endothelial cell function. We hypothesized that endogenous mechanisms protect the vasculature from excess levels of ROS. We now show that superoxide can inhibit endothelin-converting enzyme activity (ECE) and decrease endothelin-1 synthesis. Superoxide inhibits ECE but hydrogen peroxide and nitric oxide do not. Superoxide inhibits ECE by ejecting zinc from the enzyme, and the addition of exogenous zinc restores enzymatic activity. Superoxide may inhibit other zinc metalloproteinases by a similar mechanism and may thus play an important role in regulating the biology of blood vessels.
- ET-1
- endothelin-1
- ECE
- endothelin converting enzyme
- O⨪2
- superoxide anion
- ROS
- reactive oxygen species
- SOD
- superoxide dismutase
- XXO
- xanthine and xanthine oxidase
- NO
- nitric oxide
- ELISA
- enzyme-linked immunosorbent assay
- PAGE
- polyacrylamide gel electrophoresis
- BAEC
- bovine aortic endothelial cells
- Received January 31, 2000.
- Revision received May 23, 2000.
- The American Society for Biochemistry and Molecular Biology, Inc.
