ROLE OF O-LINKED CARBOHYDRATE OF HUMAN URINARY TRYPSIN-INHIBITOR ON ITS LYSOSOMAL MEMBRANE-STABILIZING PROPERTY

Human urinary trypsin inhibitor (UTI) was digested with various enzyme s to obtain O-glycoside linked N-terminal glycopeptide (UTIm1), N-glyc oside linked C-terminal tandem Kunitz-domains (domain I and II, UTIm2) , UTI lacking O-glycoside (UTIc), asialo UTI (UTIa) and UTI lacking N- glycoside (UTIn). We investigated the membrane stabilizing effect of t hese UTI derivatives on rat renal lysosome by measurement of lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG) release after hypotonic treatment. Intact UTI suppressed NAG release, but aprotinin, gabexate mesilate (FOY), nafamostat mesilate (FUT) and recombinant domain II of UTI (R-020) had no effect, indicating that inhibition of serine prote ases was not involved and the carbohydrate moiety of UTI might be nece ssary for this property. Among UTI derivatives, UTIm1, UTIm2, UTIm1+ U TIm2, and UTIc had no effect. In contrast, UTIa or UTIn suppressed NAG release. From these results, we conclude that O-glycoside linked core protein without N-glycoside is essential to the lysosomal membrane-st abilizing property of UTI. (C) 1998 Academic Press.