INDUCTION OF HEPATOCYTE PROLIFERATION AFTER PARTIAL-HEPATECTOMY IS ACCOMPANIED BY A MARKEDLY REDUCED EXPRESSION OF PHOSPHATIDYLETHANOLAMINEN-METHYLTRANSFERASE-2

Expression of phosphatidylethanolamine N-methyltransferase (PEMT)-2 in rat hepatoma cells caused an increase in the time for cell division f rom 18 to 50 h [Cui et al. (1994) J. Biol. Chem. 269, 24531-24533]. We investigated whether or not a similar inverse relationship might exis t for liver proliferation in vivo. Thus, partial hepatectomized rats w ere used to investigate the expression of PEMT2 during liver regenerat ion. Enhanced biosynthesis of phosphatidylcholine after partial hepate ctomy was due to increased activity and amount of CTP:phosphocholine c ytidylyltransferase. On the other hand the total activity of PEMT was markedly decreased during the first days of rat liver regeneration. Ma ximal decrease of total PEMT activity (45%) and loss of PEMT2 protein (90%) coincided with maximal DNA synthesis and CTP:phosphocholine cyti dylyltransferase activity 24 h after partial hepatectomy in both male and female rats. Supplementing dietary choline in the diets of female rats shifted this pattern from 24 h to 36 h after partial hepatectomy, whereas the pattern in male rats was not affected. Northern blot stud ies showed that the amount of PEMT2 mRNA was decreased accordingly, su ggesting regulation of the amount and activity of PEMT2 at a pre-trans lational level. Thus, our data show a reciprocal regulation of CTP:pho sphocholine cytidylyltransferase and PEMT2 at the level of gene expres sion in regenerating rat liver. These results implicate PEMT2 in the r egulation of hepatocyte cell growth in a physiologically relevant mode l. (C) 1997 Elsevier Science B.V.