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Maintaining high levels of intracellular cyclic AMP (cAMP) is known to inhibit the growth of various proliferating cells including hepatocytes. We show here that transient (30 min) elevations of cAMP induced by addition of 8-bromo-cAMP (1 mmol/L) to rat hepatocytes in primary culture at three time points (12 h, 16 h and 20 h) after seeding stimulated DNA synthesis. Sustained levels of cAMP stimulated DNA synthesis to a lesser degree at a lower concentration (1 mumol/L), but inhibited it at concentrations higher than 100 mumol/L. We also determined cyclin-dependent kinase 2 (cdk2) activity in the hepatocytes during this incubation period. The transient addition of 8-bromo-cAMP at the late G1 phase increased cdk2 activity. This suggests that transient cAMP elevation in hepatocytes at the late G1 phase has a growth stimulation effect. Up-regulation of cdk2 activity may have a role in this process.
M Kikukawa, and
Y Okamoto, and
H Nakano
September 1990,
Journal of cellular physiology,
M Kikukawa, and
Y Okamoto, and
H Nakano
January 1979,
Journal of cyclic nucleotide research,
M Kikukawa, and
Y Okamoto, and
H Nakano
June 1992,
Experimental cell research,
M Kikukawa, and
Y Okamoto, and
H Nakano
May 1980,
Archives of biochemistry and biophysics,
M Kikukawa, and
Y Okamoto, and
H Nakano
February 1977,
Biochemical and biophysical research communications,
M Kikukawa, and
Y Okamoto, and
H Nakano
August 1983,
Biochimica et biophysica acta,
M Kikukawa, and
Y Okamoto, and
H Nakano
November 1993,
Biochemical Society transactions,
M Kikukawa, and
Y Okamoto, and
H Nakano
October 1987,
Biochimica et biophysica acta,
M Kikukawa, and
Y Okamoto, and
H Nakano
December 1975,
Bollettino della Societa italiana di biologia sperimentale,
M Kikukawa, and
Y Okamoto, and
H Nakano
October 1980,
FEBS letters,
