ALTERATIONS IN CONSTITUENT URINARY PROTEINS IN RESPONSE TO BLADDER OUTLET OBSTRUCTION IN RATS

Purpose: Benign prostatic hyperplasia, resulting in bladder outflow ob struction, induces well recognized clinical symptoms and morphologic b ladder changes. Despite these phenomenon, relatively little is known w ith regard to the precise molecular events occurring in the bladder as a consequence of obstruction. In an effort to screen for alterations in bladder gene expression induced by obstruction, and/or alterations in uroepithelial integrity, this study compared pre- and post-obstruct ive constituent urinary proteins in an animal model. Materials and Met hods: Outlet obstruction was created using a previously established mo del system. Experimental animals were surgically obstructed for either 2 or 7 days, at which time the urine was aspirated and the bladders r emoved and weighed. Urinary proteins were separated using 2-D PAGE. Fo llowing comparison of sham versus experimental animals, microsequencin g was performed on proteins that were down regulated, Results: Duplica te experiments confirmed the presence of outflow obstruction, Statisti cally significant increases (p < 0.01) in bladder weights were seen at 2 and 7 days in the obstructed groups as compared with both sham and control groups. 2-D PAGE demonstrated a down regulation of three urina ry proteins post-obstruction. Microsequencing identified these protein s as prostatic steroid-binding protein C3 precursor (pI = 5.5, MW = 15 000), glandular kallikrein 9 (S3) precursor (pI = 6.2, MW = 19000), an d glandular kallikrein 8 (P1) precursor (pI = 6.2, MW = 33000). Conclu sions: Bladder outflow obstruction alters constituent urinary protein composition in an animal model system. The precise etiology of these a lterations remains to be defined.