Cholangiocyte-specific rat liver proteins identified by establishment of atwo-dimensional gel protein database

The liver is composed of a variety of cells that form a functional unit inv olved in uptake, synthesis, metabolism, and secretion. Until recently, most studies examining liver function did not analyze the specific proteins exp ressed or functions performed by the multiple individual cell types that co nstitute the hepatic mass. In the last decade, novel isolation methods have been developed that allow the purification of liver cell populations highl y enriched in one type of Liver cell. Here, we present a detailed two-dimen sional (2-D) protein map of rat bile duct epithelial cells (i.e., cholangio cytes) using a recently developed isolation procedure. In addition, we iden tify 27 major cholangiocyte proteins either by comparison to maps of known fat liver proteins (based on pI and M-r) or by tryptic digestion and micros equencing. Finally, we compare the relative abundance of individual protein s present in cholangiocytes to whole liver as well as hepatocyte-specific p roteins. Our results show that cholangiocytes express a unique array of ind ividual proteins. The cholangiocyte 2-D protein pattern is markedly differe nt from that of isolated rat hepatocytes or whole rat liver, with high leve ls of proteins previously known to be expressed by cholangiocytes (e.g., cy tokeratins, actins) as well as protein not previously demonstrated to be ex pressed at high levels (e.g., annexin V, selenium binding protein). We conc lude that this cholangiocyte-derived, 2-D protein map will be a crucial res ource for studies directed at our understanding of cholangiocyte physiology and pathobiology.