Altered localization and expression of the putative tight junction sealing protein occludin after common bile duct ligation. Fallon, Michael B., Alexandra R. Brecher, Maria Susana Balda, Karl Matter, and James M. Anderson. Department of Medicine, The University of Alabama Birmingham, Birmingham, Alabama 35294, Department of Medicine and the Liver Center, Yale University School of Medicine, New Haven, Connecticut 06510 and D[acute]epartement de Biologie Cellulaire, Universit[acute]e de Gen[grave]eve, Switzerland
APStracts 2:0200C, 1995.
Epithelial tight junctions form a regulated barrier which seals the paracellular space and prevents mixing of luminal contents with the interstitium. This barrier is composed of a group of proteins including the putative "sealing" protein occludin which appears to bind directly to a cytoplasmic junction protein, ZO-1. To study the interaction and regulation of these two components when paracellular integrity is altered, we assessed protein expression and immunofluorescent (IF) localization of ZO-1 and occludin in a rat model of hepatocyte tight junction damage induced by common bile duct ligation (CBDL). Protein levels were detected in liver by immunoblotting and IF localization by 3-dimensional reconstruction of serial 0.5 um confocal microscopic optical sections. As previously described, ZO-1 protein levels progressively increased to 3-fold control levels 9 days after CBDL. In contrast, occludin protein levels decreased by 50% within 2 days after CBDL and returned to control values by 9 days. In control IF sections, ZO-1 and occludin co-localized forming thin continuous staining outlining canaliculi. Following CBDL, ZO-1 staining appeared discontinuous, and a punctate peri-canalicular accumulation of signal developed around junctional areas. Occludin staining was also discontinuous after CBDL, but in contrast to ZO-1, was not punctate and remained either localized in a linear fashion along canalicular margins or in a homogeneous fashion in immediately surrounding areas. CBDL results in changes in the expression and localization of the putative tight junction sealing protein occludin in hepatocytes which are distinct from those observed for the peripheral membrane tight junction protein ZO-1. Dissociation in the expression and localization of hepatocyte tight junction components may play a role in altered tight junction function during injury. 

Received 15 March 1995; accepted in final form 5 May 1995.
APS Manuscript Number C146-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.