Identification of a novel aspartyl endothelin converting enzyme in porcine aortic endothelial cells.
An enzyme which catalyzes the conversion of proendothelin-1 to the potent vasoconstrictor peptide endothelin-1 has been identified in the detergent extract of primary porcine aortic endothelial cell membranes. Partial purification was accomplished by anion exchange and Con A affinity chromatography. The enzyme was active at pH 4 and was inhibited by 100 nM peptstatin A. Hydrolysis products of proendothelin-1 were characterized by bioassay, RIA, HPLC and molecular mass analysis. Comparisons to cathepsin D and renin demonstrated that the endothelin converting enzyme activity from the porcine aortic endothelial cells was unrelated to the known enzymes. These results suggest that the processing of proendothelin-1 by endothelial cells involves a novel pepstatin-sensitive aspartyl protease.
Knap
A K
AK
Research Department, Ciba-Geigy Corp., Summit, NJ 07901.
Soriano
A
A
Savage
P
P
Del Grande
D
D
Shetty
S S
SS
D000818:Animals; D001011:Aorta; D016282:Aspartic Acid Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D008297:Male; D008666:Metalloendopeptidases; D011498:Protein Precursors / Q000378:metabolism*; D011817:Rabbits; D011863:Radioimmunoassay; D014661:Vasoconstriction
D016232:Endothelins; D011498:Protein Precursors; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes