抄録
The activity of glucose 6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) in liver supernatant has been reported to increase both in carbon tetrachloride (CCl4)-poisoned and high carbohydratefat free diet refed rats. The increase involves the same molecular species of the enzyme. Increased incorporation of 14C-leucine into G6PD after CCl4 treatment was not affected by actinomycin D at a dose sufficient to inhibit dietary induction of the enzyme, suggesting that the mechanism of G6PD induction by liver injury appeared to differ in several aspects from that of dietary induction. In this communication, effects of glucagon, cyclic AMP and epinephrine on the level of liver G6PD were tested to obtain further evidences for the difference between these two mechanisms of G6PD induction.
Glucagon, epinephrine plus theophylline and cyclic AMP plus theophylline effectively prevented the induction of liver G6PD following the administration of glucose-casein (7: 3 by weight) to rats after 48 hr fast, although glucagon and epinephrine plus theophylline had no effect on G6PD activity in normal fasted rats. The inhibitory effect by these agents could occur without any change in the amount of diet consumed, suggesting the importance of cyclic AMP concentration in liver in dietary regulation of G6PD level. When cyclic AMP and glucose-casein diet were given simultaneously, there was an inhibition of the rate of enzyme increase depending upon the frequency of the subsequent injection of cyclic AMP, while when cyclic AMP was given later than 12 hr of refeeding, a lag period for G6PD induction, there was no inhibitory effect. This may indicate that some metabolic events occurring in the first 12 hr following the administration of diet would be blocked by cyclic AMP. We have already reported that a glucose prefeeding, which by itself caused no G6PD induction, could eliminate the lag phase as well as the inhibitory effect of actinomycin D on dietary G6PD induction. In the present study, the glucose prefeeding was also found to counteract the inhibitory effect of cyclic AMP on G6PD induction by subsequent glucose-casein refeeding. These results indicated that the inhibitory effect of cyclic AMP could not be observed if a sufficient amount of newly synthesized RNA directed to G6PD induction was already available through a prior glucose feeding. Thus, the effect of cyclic AMP appears to be exerted at the level of transcription.
In contrast to the dietary induction of G6PD, the induction by CCl4-mediated liver injury was shown to be essentially insensitive to glucagon. This is consistent with already reported facts that liver G6PD induction by CCl4 liver injury is due to an altered mechanism of posttranscriptional regulation of the enzyme synthesis, probably at the level of translation. It is thus interesting to investigate how altered functions of the polyribosomes in CCl4-injured liver may participate to G6PD induction. The prior administration of ethyl D-glucofururonoside p-ethoxyphenylhydrazide (CG-DOL)
