Major loss of the 28-kD protein of gap junction in proliferating hepatocytes.

Abstract

Abstract. There is a reduction in the 28-kD gap junction protein detectable by immunofluorescence in livers of partially hepatectomized rats and in cultured hepatocytes stimulated to proliferate. By the coordinate use of antibodies directed to the hepatic junction protein (HJP28) and the use of a monoclonal antibody that recognizes bromodeoxyuridine (BrdU) incorporated into DNA, we have been able to study the relationship between detectable gap junction protein and cell division. Hepatocytes that label with BrdU in the regenerating liver and in cell culture show a significant reduction of HJP28. Cells that do not synthesize DNA, on the other hand, show normal levels and distribution of immunoreactive gap junction protein. We postulate that the quantitative changes in gap junction expression might play an important role in the control of proliferation in the liver.AP junctions represent a class of intercellular contacts which are commonly assumed to be the site of exchange of inorganic ions and small molecules (3,4,14,35). It has been suggested that they may be involved in regulating various cellular activities such as growth control (7,27), and the modulation of developmental processes during embryogenesis (19,38,39,44). There is a close correlation between the ultrastructural demonstration of gap junctions and the presence of cell-cell coupling measured electrophysiologically or by injection of fluorescent dyes (2, 14, 36). Several laboratories have recently reported the characterization of antibodies directed against the 28-kD protein that is a major component of isolated rat liver gap junctions (hepatic junction protein, HJP28) ~ (9,20,23,24,32,42). Intracellular injection of specific antibodies raised against rodent HJP28 inhibits electrical or dye-coupling between several types of vertebrate cells (21, 28). Injection of antibodies raised against this protein into blastomeres of Xenopus appears to cause developmental defects in the larva (43). These antibodies thus detect a functionally competent form of HJP28.The regenerating liver is an interesting experimental model where the possible correlation between gap junctions and the control of growth can be examined (12,29,41,45,46). Partial hepatectomy causes a burst of cell division that, by morphometric studies of freeze-cleaved material, has been shown to be temporally correlated with a cycle of disappearance and reappearance of gap junctions (45, 46). A significant reduction of the HJP28 has also been seen after partial hepatectomy by biochemical and immunochemical criteria (12, 41). Abbreviations used in this paper:BrdU, bromodeoxyuridine; HJP, hepatic junction protein.Not all cells participate in this wave of cell proliferation (34) nor is there a complete loss of junctional communication (29). Until now it has not been possible to establish a definite link between cell division and the loss of gap junction. The experiments described here use a double-immunolabeling approach to the study of regenerating liver cells and of cultured primary hepatocytes from...

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