Superoxide regulation of endothelin-converting enzyme.
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.
López-Ongil
S
S
Divisions of Cardiology and Nephrology, the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Senchak
V
V
Saura
M
M
Zaragoza
C
C
Ames
M
M
Ballermann
B
B
Rodríguez-Puyol
M
M
Rodríguez-Puyol
D
D
Lowenstein
C J
CJ
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism; D000072396:Endothelin-Converting Enzymes; D004730:Endothelium, Vascular / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008666:Metalloendopeptidases; D009569:Nitric Oxide / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*; D019820:Xanthine / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
D019332:Endothelin-1; D017382:Reactive Oxygen Species; D013481:Superoxides; D019820:Xanthine; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D015032:Zinc