TRANSIENT INACTIVATION OF PHOSPHATIDYLETHANOLAMINE N-METHYLTRANSFERASE-2 AND ACTIVATION OF CYTIDINE TRIPHOSPHATE - PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE DURING NONNEOPLASTIC LIVER GROWTH

Phosphatidylethanolamine N-methyltransferase-2 (PEMT2) may contribute to the control of hepatocyte cell division, since its inactivation is associated with several types of liver proliferation including tumorig enesis [Cui, Houweling and Vance (1994) J. Biol. Chem. 269, 24531-2453 3]. To determine if the inactivation of PEMT2 was involved in non-neop lastic proliferation of hepatocytes, we studied the expression of this enzyme in a model of lead nitrate-induced liver proliferation in vivo in rats. A maximal decrease in PEMT activity (60 %) and loss of PEMT2 protein (95%) coincided with maximal DNA synthesis and maximal cytidi ne triphosphate:phosphocholine cytidylyltransferase activity 36 h and 48 h after lead nitrate stimulation in male and female livers respecti vely. The decrease in expression of PEMT2 corresponded to a decrease i n its mRNA. Compared with males, female rats exhibited a 12 h delay in the peak of DNA synthesis, in cytidylyltransferase activity and in th e minimum of PEMT2 expression. Supplementation of the rats with dietar y choline shifted the female pattern of PEMT2 inactivation, DNA synthe sis and activation of cytidylyltransferase to 12 h earlier so that it was similar to the time frame of the expression of these activities in males. These results are consistent with the proposal that the inacti vation of PEMT2 may have a role in the regulation of non-neoplastic gr owth of liver.