Protective protein as an endogenous endothelin degradation enzyme in human tissues

Abstract

An enzyme hydrolyzing the carboxyl terminus of endothelin-1 was detected in control human tissues but was deficient in tissues from a patient with galactosialidosis, a metabolic disease caused by the protective protein gene mutation. It was proportional to the amount of immunologically estimated mature protective protein. An antibody against the lysosomal protective protein/β-galactosidase complex precipitated the enzyme activity almost completely. Transfection of the human cDNA for protective protein resulted in high expression of the enzyme activity in transformed fibroblasts from a galactosialidosis patient. These results indicated that the mature protective protein is a major soluble endogenous endothelin degradation enzyme in human tissues.