Stabilization of ornithine decarboxylase in mouse liver and lung by methylglyoxal bis(cyclohexylamidinohydrazone)

Abstract

The intraperitoneal injection of methylglyoxal bis(cyclohexylamidinohydrazone) (MGBC), an inhibitor of S-adenosylmethionine decarboxylase and spermidine synthase, markedly increased (7-fold of the basal level at 4 hr) ornithine decarboxylase (ODC) activity in normal mouse liver. ODC activity was also increased 2.5-fold over the basal level in mouse lung at 6 hr after the injection. The effect of MGBC on ODC activity occurred in a dose-dependent manner. Measurement of the apparent half-life of ODC induced in the liver and lung by MGBC treatment revealed a clear decrease in the decay rate of the enzyme in both the tissues. Activities of S-adenosylmethionine decarboxylase (AdoMetDC) and spermidine/spermine N 1-acetyltransferase (SAT) were not increased by the intraperitoneal injection of MGBC. There was a large rise in putrescine and a fall in spermidine and spermine in the liver and lung except for brain within an 8 hr period in response to MGBC, suggesting that these changes resulted from the stabilization of ODC and inhibitions of AdoMetDC and spermidine synthase.