ROLE OF PROTEIN-KINASE-A IN HUMAN HEPATOCYTE DNA-SYNTHESIS

The cellular mechanisms associated with the replicative response of he patocytes to growth factor stimulation is incompletely understood, Mur ine hepatocyte DNA synthesis is altered by cyclic AMP, suggesting that protein kinase A is involved in the cellular mechanisms associated wi th liver growth. The purpose of this study was to evaluate the role of protein kinase A in human hepatocyte DNA synthesis. Human hepatocytes were isolated and maintained in primary culture on rat tail collagen. DNA synthesis was evaluated by determining [H-3]thymidine incorporati on, Human hepatocytes between 24 and 96 hr following harvest increased DNA synthesis in response to epidermal growth factor but not in respo nse to glucagon, a stimulant of adenyl cyclase, or dibutyryl cyclic AM P. Mitogen-stimulated DNA synthesis was decreased by dibutyryl cyclic AMP, Cyclic AMP isomers that block or stimulate the effect of cyclic A MP on protein kinase A did not significantly alter resting or mitogen- stimulated human hepatocyte DNA synthesis. The results suggest that in creased protein kinase A activity does not produce human hepatocyte re plicative DNA synthesis.