Nature of the increase in renal ornithine decarboxylase activity after cycloheximide administration in the rat.

Abstract

The present study was designed to determine whether the increase in rat renal ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity after cycloheximide administration was a primary effect on the kidney or was a secondary effect of adrenal or pituitary hormones released in response to the drug. Renal ornithine decarboxylase activity was reduced approximately 70% 1 hr after intraperitoneal administration of doses of cycloheximide that also inhibited renal protein synthesis by 68-95% within 1 hr. Protein synthesis began to recover by the second hour, accompanied by a rise in decarboxylase activity that reached a peak about six times greater than pretreatment values at 8 hr, then gradually declined to preinjection levels by 16 hr. Peak ornitlhine decarboxylase activity was directly proportional to cycloheximide doses up to 250 Mg; larger doses, which almost abolished protein synthesis for 8 hr, were inhibitory. Plasma corticosterone rose rapidly after cycloheximide, reached a peak at 2 hr, then fell to baseline by 8 hr. Corticosterone response was also dose-dependent up to 250 Mg, but larger doses were inhibitory. Adrenalectomy did not reduce decarboxylase activity response to cycloheximide, nor did cortisol administration enhance it. Hypophysectomy greatly reduced baseline renal decarboxylase activity within 9 hr and all but abolished the increase in enzyme activity normally seen after cycloheximide administration to the intact rat. The hypophysectomized animal exhibited apparent increased sensitivity to cyclohieximide, since a smaller dose of the drug caused a reduction in renal protein synthesis similar to that seen with a larger dose in the intact rat. As protein synthesis was recovering in the hypophysectomized animals, renal decarboxylase activity responded adequately to the injection of a crude pituitary extract. These data suggest that renal ornithine decarboxylase turnover is rapid, that baseline activity is maintained by new protein synthesis, and that the increase in renal enzyme activity after cyclolieximide is in large part dependent upon pituitary hormone action.

Regulation of mammalian protein synthesis in vivo. Protein synthesis in rat liver and kidney after the administration of sublethal doses of cyclohyximide

“…The results presented here do not shed light on possible hormonal changes, which might be invoked after cycloheximide administration (Levine et al, 1975) and which might influence the interpretation of this study. However, the investigations by Christopher et al (1971) using cells in tissue culture seem to eliminate a direct correlation between changes in hormone concentrations and the rate of protein synthesis after the administration of cycloheximide.…”

“…Histones were prepared by extracting chromatin with ice-cold 0.2M-HASO4. Levine et al, 1975). After the inhibition of protein synthesis, HeLa cells in culture show an increased rate of initiation (Penman et al, 1973).…”

Inhibitory effect of various cytostatics and cycloheximide on acute experimental pancreatitis in rats.

“…It interferes with the synthesis of proteins on cytoplasmatic ribosomes (Baliga et al, 1969); however, care must be taken in interpreting its inhibitory effects (Timberlake and Griffin, 1974). After the administration of this antibiotic the activity of several enzymes was found to be enhanced (Cihak, 1975;Levine et al, 1975). 5-Azacytidine, successfully used in the treatment of acute leukaemia in childhood (Hrodek and Vesely, 1971), has a polyvalent inhibitory mechanism (tihaik, 1974).…”