HISTIDASE EXPRESSION IS REGULATED BY DIETARY-PROTEIN AT THE PRETRANSLATIONAL LEVEL IN RAT-LIVER

The effect of dietary protein on the expression of histidase (Hal) was investigated to understand the mechanism of induction of histidase by a high protein diet. In this study, we examined the following: 1) the effect of 0, 6, 18, 35 and 50% casein diets on hepatic and epidermal Hat activity, amount of the enzyme and Hal-mRNA; 2) the effect of a hi gh histidine diet (1.25%) on Hal expression; 3) the response of Hal ex pression in rats fed a 10% casein diet and injected with glucagon (0.6 mg /(100 g body wt.d); and 4) the half-lives of the enzyme and Hal-mR NA in rats fed an 80% casein diet for 7 d followed by a protein-free d iet. Hal activity increased as the protein content in the diet increas ed (r = 0.986, P < 0.001) and was associated with a significant increa se in V-max without a change in K-m. The dietary regulation was liver specific because skin Hat was unresponsive. Increments in hepatic Hal activity were accompanied by concomitant significant increases in the amount of histidase and its mRNA. The response was more pronounced in rats fed diets containing >18% casein. Rats fed a 12% casein diet cont aining 1.25% histidine did not have different Hal activity and mRNA le vels compared with rats fed a 12% casein diet, indicating that Hal exp ression is not modified by its substrate. Injection of glucagon into r ats fed the 10% casein diet increased Hal activity threefold and Hal-m RNA expression fivefold compared with uninjected rats fed the same die t. The apparent half-life of hepatic histidase in protein-depleted rat s previously fed an 80% casein diet was 2.8 d, whereas the half-life o f Hal-mRNA was 17 h. In summary, these data support the hypothesis tha t Hal expression is regulated by dietary protein at the pretranslation al level in rat liver, and that glucagon is one of the hormones involv ed in the induction of Hal.