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Effects of gamma-irradiation on biosynthesis of different types of ribonucleic acids in normal and regenerating rat liver.

ABSTRACT: 1. The effect of gamma-irradiation (4000rd) on the synthesis of ribosomal (pre-rRNA) and heterogeneous nuclear RNA (pre-mRNA) in normal and in regenerating rat liver was studied by using 40 min labelling with [6(-14)C]orotic acid. 2. Partial hepatectomy caused a sharp transient increase in the specific radioactivity of the endogenous low-molecular-weight RNA precursors in the livers of both normal and irradiated rats. Irradiation of intact animals did not affect the pool. 3. Irradiation enhanced the synthesis of pre-rRNA for at least 12h. The synthesis of pre-mRNA was also enhanced, but only in the first 3h after irradiation. 4. Partial hepatectomy strongly stimulated the synthesis of both pre-rRNA and pre-mRNA. 5. The synthesis of pre-rRNA was enhanced also in regenerating liver of animals irradiated before or after the operation. The conclusion can be drawn that the early increase in the synthesis of ribosomal RNA is a non-specific cellular response to different injuring factors. 6. The only case where irradiation caused an early inhibition of RNA synthesis was that of pre-mRNA in regenerating liver. This supports the hypothesis that ionizing radiation does not suppress the transcription per se but affects the mechanisms of activation of new genes (cellular programming).

SUBMITTER: Markov GG

PROVIDER: S-EPMC1165274 | biostudies-other | 1975 Jan

REPOSITORIES: biostudies-other

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Project description:The ability of the liver to regenerate and adjust its size after two/third partial hepatectomy (PH) is impaired in old rodents and humans. Here, we investigated by microarray analysis the expression pattern of hepatic genes in young and old untreated mice and the differences in gene expression profile following PH. Of the 10,237 messenger RNAs that had detectable expression, only 108 displayed a greater than 2-fold modification in gene expression levels between the two groups. These genes were involved in inflammatory and immune response, xenobiotics, and lipid and glucose metabolism. To identify the genes responsible for the different regenerative response, 10-week and 18-month-old mice subjected to PH were sacrificed at different time intervals after surgery. The results showed that 2463 transcripts had significantly different expression post PH between the two groups. However, in spite of impaired liver regeneration in old mice, cell cycle genes were similarly modified in both groups, the only exception being cyclin D1 gene which was up-regulated soon after PH in young mice, but mostly down-regulated in aged animals. Surprisingly, while in young hepatectomized mice, Yap messenger RNA (mRNA) expression was not significantly enhanced and protein expression essentially reflected the progression into cell cycle, its mRNA and protein levels were robustly increased in the liver of aged animals. Furthermore, a significant change of the age-related expression of the size regulator Yes-associated protein (YAP) was observed. Unexpectedly, while in young hepatectomized mice, Yap mRNA expression was not significantly enhanced and protein expression essentially reflected the progression into cell cycle, its mRNA and protein levels were robustly increased in the liver of aged animals. Moreover, when PH was performed on mitogen-induced enlarged livers, the earlier restoration of the original liver mass compared to animals subjected to PH only led to YAP down-regulation concomitantly with cyclin D1 up-regulation. Our data suggest that YAP activation is a size-dependent homeostatic mechanism that does not necessarily reflect cell cycle progression.

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Effects of gamma-irradiation on biosynthesis of different types of ribonucleic acids in normal and regenerating rat liver.

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