title: Role of protein kinase A in human hepatocyte DNA synthesis.
abstract: The cellular mechanisms associated with the replicative response of hepatocytes to growth factor simulation is incompletely understood. Murine hepatocyte DNA synthesis is altered by cyclic AMP, suggesting that protein kinase A is involved in the cellular mechanisms associated with 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 [3H] thymidine incorporation. Human hepatocytes between 24 and 96 hr following harvest increased DNA synthesis in response to epidermal growth factor but not in response to glucagon, a stimulant of adenyl cyclase, or dibutyryl cyclic AMP. Mitogen-stimulated DNA synthesis was decreased by dibutyryl cyclic AMP. Cyclic AMP isomers that block or stimulate the effect of cyclic AMP on protein kinase A did not significantly alter resting or mitogens-stimulated human hepatocyte DNA synthesis. The results suggest that increased protein kinase A activity does not produce human hepatocyte replicative DNA synthesis.
authors.affiliation: Department of Surgery, St. Louis University Hospital, Missouri 63110-0250, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Kaminski
authors.forename: M A
authors.initials: MA
authors.lastname: Roque
authors.forename: A P
authors.initials: AP
authors.lastname: Li
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
chemical_list: D014316:Tritium; D004247:DNA; D017868:Cyclic AMP-Dependent Protein Kinases; D013936:Thymidine