Hormonal control of hyaluronic acid production in fibroblasts and its relation to nucleic acid and protein synthesis.

Whole serum and elevated pH previously had been found to stimulate both cell multiplication and hyaluronic acid production by chick embryo fibroblasts in culture. In a study to determine whether cell multiplication and hyaluronic acid production both respond to a single well-defined substance, insulin was found to stimulate, and cortisol to inhibit both processes coordinately. It appears, therefore, that multiplication and differentiated function in fibroblasts respond to a common underlying regulatory signal. Inhibition of ribosomal RNA synthesis by actinomycin D does not prevent serum stimulation of hyaluronic acid production, but inhibition of total RNA synthesis does. If total RNA synthesis is inhibited only after the hyaluronic acid production has reached a new high level, it continues at that level for the next five hours. The stimulatory treatment causes an increase in the activity of the enzyme hyaluronate synthetase. Inhibition of protein synthesis prevents any increase in hyaluronic acid production, and reduces the basal level of production. Reduction of the availability of Mg2+ in the medium coordinately inhibits DNA synthesis and hyaluronic acid production. The results are discussed in the light of a model for coordinate control growth and metabolism based on the availability of Mg2+.     

珍奥酵母核酸对环磷酰胺致小鼠免疫功能低下的影响

目的 通过环磷酰胺致小鼠免疫功能低下,建立BALB/C小鼠免疫功能低下模型,评价珍奥酵母核酸对小鼠免疫功能低下的作用.方法 选用BALB/C小鼠,随机分组,分别给予相应的处理,选择T淋巴细胞亚群CD69+/CD3+比值、NK细胞亚群CD69+/NKG2D+比值、淋巴细胞转化率及血清IL-2含量作为细胞免疫的指标.结果 核酸各剂量组和添加剂组均可使免疫低下小鼠外周血和脾的T淋巴细胞亚群CD69+/CD3+比值、NK细胞亚群CD69+/NKG2D+比值提高,同时可提高免疫低下小鼠淋巴细胞转化率及IL-2水平,尤以高、中剂量核酸组和添加剂组明显(P＜0.05).结论 珍奥酵母核酸可以提高免疫低下小鼠的免疫功能,以其为珍奥酵母核酸的临床应用及提高机体免疫力提供了实验依据.     

The improbability of prebiotic nucleic acid synthesis

Many accounts of the origin of life assume that the spontaneous synthesis of a self-replicating nucleic acid could take place readily. Serious chemical obstacles exist, however, which make such an event extremely improbable.Prebiotic syntheses of adenine from HCN, of D, L-ribose from adenosine, and of adenosine from adenine and D-ribose have in fact been demonstrated. However these procedures use pure starting materials, afford poor yields, and are run under conditions which are not compatible with one another.Any nucleic acid components which are formed on the primitive earth would tend to hydrolyze by a number of pathways. Their polymerization would be inhibited by the presence of vast numbers of related substances which would react preferentially with them.It appears likely that nucleic acids were not formed by prebiotic routes, but are later products of evolution.     

The improbability of prebiotic nucleic acid synthesis

Many accounts of the origin of life assume that the spontaneous synthesis of a self-replicating nucleic acid could take place readily. Serious chemical obstacles exist, however, which make such an event extremely improbable. Prebiotic syntheses of adenine from HCN, of D,L-ribose from adenosine, and of adenosine from adenine and D-ribose have in fact been demonstrated. However these procedures use pure starting materials, afford poor yields, and are run under conditions which are not compatible with one another. Any nucleic acid components which were formed on the primitive earth would tend to hydrolyze by a number of pathways. Their polymerization would be inhibited by the presence of vast numbers of related substances which would react preferentially with them. It appears likely that nucleic acids were not formed by prebiotic routes, but are later products of evolution.     

The inhibition of nucleic acid synthesis by mycophenolic acid

1. Mycophenolic acid, an antibiotic of some antiquity that more recently has been found to have marked activity against a range of tumours in mice and rats, strongly inhibits DNA synthesis in the L strain of fibroblasts in vitro. 2. The extent of the inhibition of DNA synthesis is markedly increased by preincubation of the cells with mycophenolic acid before the addition of [(14)C]thymidine. 3. The inhibition of DNA synthesis by mycophenolic acid in L cells in vitro is reversed by guanine in a non-competitive manner, but not by hypoxanthine, xanthine or adenine. 4. The reversal of inhibition by guanine can be suppressed by hypoxanthine, 6-mercaptopurine and adenine. 5. Mycophenolic acid does not inhibit the incorporation of [(14)C]thymidine into DNA in suspensions of Landschütz and Yoshida ascites cells in vitro. 6. Mycophenolic acid inhibits the conversion of [(14)C]hypoxanthine into cold-acid-soluble and -insoluble guanine nucleotides in Landschütz and Yoshida ascites cells and also in L cells in vitro. There is some increase in the radioactivity of the adenine fraction in the presence of the antibiotic. 7. Mycophenolic acid inhibits the conversion of [(14)C]hypoxanthine into xanthine and guanine fractions in a cell-free system from Landschütz cells capable of converting hypoxanthine into IMP, XMP and GMP. 8. Preparations of IMP dehydrogenase from Landschütz ascites cells, calf thymus and LS cells are strongly inhibited by mycophenolic acid. The inhibition showed mixed type kinetics with K(i) values of between 3.03x10(-8) and 4.5x10(-8)m. 9. Evidence was also obtained for a partial, possibly indirect, inhibition by mycophenolic acid of an early stage of biosynthesis of purine nucleotides as indicated by a decrease in the accumulation of formylglycine amide ribonucleotide induced by the antibiotic azaserine in suspensions of Landschütz and Yoshida ascites cells and L cells in vitro.     

Effect of adrenocorticotropic hormone on nucleic acid and protein synthesis and content in the brain of rat embryos in the early stages of neurogenesis]

The injection of adrenocorticotropic hormone (ACTH) of prolonged effect at the doses of 4 and 10 M. U. to the intact rats from the 11th till the 15th day of pregnancy resulted in the twofold increase of protein content in the brain and its decrease in the liver of 15 days old embryos, as compared with the control ones. The content of DNA, RNA and proteins in the placenta of experimental animals increased as well. The rate of incorporation of 3H-thymidine in the liver DNA and 14C-leucine in the liver and brain acid-soluble protein decreased within small intervals of time following the treatment. The total radioactivity of proteins in the liver, brain and placenta calculated per DNA unit was similar to the control one whereas the specific radioactivity of total protein in the liver of experimental embryos was higher than in the control.