Role of protein kinase a in human hepatocyte DNA synthesis |
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Authors: | Dr D L Kaminski MD M A Roque MS A P Li PhD |
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Institution: | (1) From the Department of Surgery, St. Louis University Hospital, 3635 Vista Ave. at Grand Blvd., P.O. Box 15250, 63110-0250 St. Louis, Missouri |
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Abstract: | The cellular mechanisms associated with the replicative response of hepatocytes to growth factor stimulation 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 mitogen-stimulated human hepatocyte DNA synthesis. The results suggest that increased protein kinase A activity does not produce human hepatocyte replicative DNA synthesis.Supported in part by USPHS DK27695. |
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Keywords: | hepatocytes DNA synthesis cyclic AMP protein kinase A |
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