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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:2192.)
© 2003 American Heart Association, Inc.

Vascular Biology

Nuclear Localization of Endothelin-Converting Enzyme-1

Subisoform Specificity

Farahdiba Jafri; Adviye Ergul

From the Clinical and Experimental Therapeutics Program, University of Georgia and Vascular Biology Center, Medical College of Georgia, Augusta, GA.

Correspondence to Adviye Ergul, MD, PhD, Medical College of Georgia, Clinical Pharmacy CJ-1020, Augusta, Georgia 30912. E-mail aergul{at}mail.mcg.edu

Objective— The biosynthesis of endothelin-1 (ET-1), the most potent vasoconstrictor with mitogenic properties, involves the processing of intermediate protein big ET-1 by a unique metalloprotease, endothelin-converting enzyme-1 (ECE-1). ECE-1 has 4 subisoforms that possess the same catalytic properties but different localization patterns on the plasma membrane and cytosol. We investigated the trafficking of ECE-1 subisoforms using green fluorescent protein–tagged recombinant enzymes in target and nontarget cells.

Methods and Results— ECE-1 localization was studied using confocal microscopy, which provides evidence for the first time that both ET-1 and ECE-1a are also found in the nuclear compartment in transiently transfected cells as well as in native endothelial cells that endogenously possess the ET system. In cells maintained in high-glucose medium, ECE-1a–specific staining shifted from plasma membrane to intracellular compartments. ECE-1b subisoform, however, is mainly in the cytosolic compartment, indicating a subisoform specificity for nuclear localization.

Conclusions— Our findings define a novel localization pattern for the ET system, which may be differentially regulated under pathophysiological conditions.

Key Words: endothelin • subcellular localization • high glucose

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