The synthesis of various types of ribonucleic acid (RNA) isolated from 6- to 3-month-old female Fischer F344 rats was compared. The rate of RNA synthesis by freshly prepared hepatocytes was determined by dividing the amount of [3H]orotic acid incorporated into RNA as uridine-5'-monophosphate by the specific activity of the uridine-5'-triphosphate pool. The rate of total RNA synthesis by hepatocytes from 19-month-old rats was 40% less than the rate for hepatocytes from 12-month-old rats. No significant difference in the rate of total RNA synthesis was observed between 19 and 30 months of age. The percentage of [3H]orotic acid incorporated into poly(A) + RNA by 30-month-old rats was approximately 50% less than that observed for hepatocytes isolated from 6-month-old rats. The percentage of [3H]orotic acid incorporated into poly(A)-RNA as ribosomal RNA (38S, 18S, and 5S RNAs) or transfer RNA was similar for 12- and 30-month-old rats. The rate of poly(A) + RNA synthesis by hepatocytes isolated from 30-month-old rats was 65% less than that observed for hepatocytes from 6-month-old rats. In contrast to total RNA synthesis, the rate of poly(A) + RNA synthesis for the 30-month-old rats was significantly less than the rate for 19-month-old rats.
The influence of age and food restriction on kidney protein synthesis was studied in Fischer F344 rats. The rate of total protein synthesis by suspensions of kidney cells declined 60% between 4 and 31 months of age. The rate of protein synthesis by kidney cells isolated from 19-month old rats fed a restricted diet (60% of diet consumed by rats fed ad libitum) was 45% higher than the rate of protein synthesis by kidney cells isolated from 19-month old rats fed ad libitum. The excretion of protein in the urine was measured to assess the effect of the age related decline in protein synthesis on kidney function. A dramatic increase in proteinuria was observed with increasing age, and rats fed the restricted diet excreted significantly less protein in the urine than rats fed ad libitum.
Remarkable similarities in the intracellular and genetic events occur when lymphoid and hematopoietic cells are exposed to their specific growth factors. The interleukin-2 (IL-2) receptor, whose cell-surface expression is an absolute requirement for the growth and differentiation of lymphoid cells, was detected on various nonlymphoid hematopoietic cell types in this study. Cell lines consisting either of granulocyte-macrophage precursors or mast cells, which are dependent on interleukin-3 (IL-3) for their growth, expressed high levels of the IL-2 receptor on their surface. Analysis of the binding characteristics of these receptors with 125I-labeled recombinant IL-2 revealed that only receptors with low affinity for IL-2 were present on these cells. Addition of purified recombinant IL-3 to these cell lines led to an increase in IL-2 receptor gene expression within 1 hour in isolated nuclei. This IL-3--induced increase in the number of IL-2 receptors on the cell surface is maximal within 24 hours. Addition of 10,000 units of IL-2 to these cells had no apparent effect on their growth or differentiation. The presence of the receptor with only low affinity for IL-2 on hematopoietic cells and the regulation by IL-3 suggest that this receptor is involved in some important metabolic event in hematopoiesis.
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