The effect of hepatocyte growth factor on ornithine decarboxylase activity was studied in primary cultured adult rat hepatocytes. Ornithine decarboxylase activity was increased 3 hr after the addition of hepatocyte growth factor and remained at a high level until 12 hr; thereafter it decreased, and it returned to the control level by 24 hr. Enzyme activity began to increase with 1 ng/ml hepatocyte growth factor and reached its maximum with 5 ng/ml hepatocyte growth factor. When insulin or epidermal growth factor was added with hepatocyte growth factor, enzyme activity was further stimulated. The level of ornithine decarboxylase messenger RNA did not increase with addition of hepatocyte growth factor. The half-time of ornithine decarboxylase activity was prolonged about twofold by hepatocyte growth factor treatment. These results suggest that hepatocyte growth factor treatment of cells enhanced ornithine decarboxylase activity posttranslationally (HEPATOLOGY 1993;17:99-102.)
The polyamines putrescine, spermidine and spermine are widely distributed in many different cells and play an essential role in cell growth and differentiation (1). Cellular polyamine levels and levels of their corresponding biosynthetic enzymes, such as ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase, increase during the early phase of cell growth and development. ODC is the first and rate-limiting enzyme in polyamine biosynthesis in mammalian cells, and it rapidly responds to hormones, growth factors and other stimuli (2). Thus ODC is important in the control of cell growth and differentiation in many types of cells.
Hepatocyte growth factor (HGF) was found in the sera of partially hepatectomized rats (3) and purified to homogeneity from rat platelets (4, 5). It is a potent mitogen for mature hepatocytes in primary culture. HGF induced rapid tyrosine phosphorylation of proteins in intact target cells, suggesting that a protein tyrosine