Modification of sarcolemmal phosphatidylethanolamine N-methylation during heart hypertrophy

To evaluate changes in heart sarcolemmal phosphatidylethanolamine (PE) N-methylation, left ventricular hypertrophy was induced in rabbits by banding the abdominal aorta for 4, 8, 14, and 22 wk. The degree of cardiac hypertrophy did not change over the period of time studied. Three catalytic sites involved in the sequential methyl transfer reactions were examined by assaying the incorporation of radiolabeled methyl groups from S-adenosyl-L-methionine (0.055, 10, and 150 microM) into sarcolemmal PE molecules under optimal conditions. Total N-methylation activity at all three sites was significantly increased at 4 wk, unaltered at 8 and 14 wk, and depressed at 22 wk after banding the aorta. Similar biphasic changes were seen for the individual methylated lipid products (monomethylphosphatidylethanolamine, dimethylphosphatidylethanolamine, and phosphatidylcholine) specifically formed at each catalytic site. At all three sites, alterations in PE N-methylation at 22 wk were associated with changes in Vmax values without any change in the apparent affinity for S-adenosyl-L-methionine. In contrast to sarcolemma, a significant increase of the PE N-methylation activity at sites I and III was observed in the sarcoplasmic reticular (microsomal) fraction from 22-wk hypertrophied hearts; the increase in site II was not significant. On the other hand, no changes in the N-methylation activity of the mitochondrial fraction were seen at 22 wk after banding. These findings indicate the occurrence of biphasic alterations in the sarcolemmal PE N-methylation activity during the presence of a stable degree of hypertrophy.