Polyamines, ribonucleases, and the stability of RNA

Karpetsky, Timothy P.; Hieter, Philip; Frank, Joseph J.; Levy, Carl C.

doi:10.1007/bf01743432

Cited by 32 publications

(13 citation statements)

References 119 publications

(3 reference statements)

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“…On the basis of in vitro studies, the polyamines have been implicated in the regulation of virtually every step of the synthesis and degradation of RNA [147]. The relative importance, within the cell, of each of these interactions, remains elusive.…”

Section: E) Role Of Polyamines In Rna Synthesismentioning

confidence: 99%

Role of Polyamines in the Control of Cell Proliferation and Differentiation

1981

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Section: E) Role Of Polyamines In Rna Synthesismentioning

confidence: 99%

Role of Polyamines in the Control of Cell Proliferation and Differentiation

1981

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“…It is now well established that polyamines modulate activities of RNA polymerases when studied in systems in vitro (Blair,19S5). The polyamines also influence the stability of RNA in vitro by binding directly to RNA or by interacting with enzymes that degrade RNA molecules (Karpetsky et al, 1977). However, the findings of studies in vivo have been far from conclusive as far as a direct relationship between the metabolism of polyamines and that of RNA is concerned (Goyns, 1982).…”

Section: Introductionmentioning

confidence: 99%

A role for polyamines in glucose-stimulated insulin-gene expression

Welsh

1990

Biochemical Journal

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The aim of the present study was to evaluate the possible role for polyamines in the glucose regulation of the metabolism of insulin mRNA of pancreatic islet cells. For this purpose islets were prepared from adult mice and cultured for 2 days in culture medium RPMI 1640 containing 3.3 mm-or 16.7 mM-glucose with or without the addition of the inhibitors of polyamine biosynthesis difluoromethylornithine (DFMO) and ethylglyoxal bis(guanylhydrazone) (EGBG). Culture at the high glucose concentration increased the islet contents of both insulin mRNA and polyamines. The synthesis of total RNA, total islet polyamines and polyamines associated with islet nuclei was also increased. When the combination of DFMO and EGBG was added in the presence of 16.7 mM-glucose, low contents of insulin mRNA, spermine and spermidine were observed. Total islet polyamine synthesis was also depressed by DFMO + EGBG, unlike islet biosynthesis of polyamines associated with nuclei, which was not equally decreased by the polyamine-synthesis inhibitors. Total RNA synthesis and turnover was not affected by DFMO + EGBG. Finally, actinomycin D attenuated the glucoseinduced enhancement of insulin mRNA, and cycloheximide counteracted the insulin-mRNA attenuation induced by inhibition of polyamine synthesis. It is concluded that the glucose-induced increase in insulin mRNA is paralleled by increased contents and rates of polyamine biosynthesis and that an attenuation of the increase in polyamines prevents the increase in insulin mRNA. In addition, the results are compatible with the view that polyamines exert their effects on insulin mRNA mainly by increasing the stability of this messenger. INTRODUCTIONIt is generally agreed that glucose is the principal regulator of the insulin gene (Welsh, 1989). This nutrient is thought to increase insulin mRNA contents both in vitro and in vivo, and increases of as much as 10-fold have been observed on glucose stimulation (Brunstedt & Chan, 1982). The glucose effect is mediated by a combination of increased transcription of the insulin gene and a selective stabilization of insulin mRNA against degradation . The stimulatory effect of glucose on insulin-gene transcription may, in part, be mediated by cyclic AMP Welsh et al., 1985). It has been shown that other nutrients also enhance insulin-gene expression (Welsh et al., 1986) and that the insulin mRNA contents often correlate well with the rate of islet ATP generation (Welsh et al., 1986;Spinas et al., 1987;Eizirik et al., 1988). Thus glucose may need to be metabolized in order to exert its effects on insulin-gene expression; however, the precise role of the putative factors produced by glucose metabolism in this mechanism remains unknown.Polyamines are ubiquitous aliphatic cations present at millimolar concentrations in pancreatic f-cells (Hougaard et al., 1986; Welsh & Sj6holm, 1988 (Howell & Taylor, 1968;Lernmark et al., 1976). The islets were subsequently picked free from exocrine tissue and maintained free-floating in tissue culture at 37°C under a humidifi...

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“…In several studies, using polyamine-depleted cells, it was found that the interference with DNA synthesis was the re sult of a decrease in DNA chain initiation rather than reduced DNA chain elongation [14,15], The results of Geiger and Morris [ 16,17], however, suggest that polyamine defi ciency results in a markedly reduced rate of DNA replication fork movement and not in a decreased initiation frequency. The relative importance of polyamines for RNA synthesis remains elusive although in vitro data suggest a role in the regulation of almost every step of the synthesis and degradation of RNA [18]. Moreover, polyamines have been implicated in the stimulation of mRNA transcription and translation [19].…”

Section: The Role O F Polvamines In Perireplicative Eventsmentioning

confidence: 99%

Diamine Oxidase: An Overview of Historical, Biochemical and Functional Aspects

Wolvekamp

Bruin²

1994

Dig Dis

160

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This article is a review of the historical, biochemical, and functional aspects of the enzyme diamine oxidase (DAO). The amine oxidase DAO, formerly called histaminase, is found in various tissues, but is especially active in the intestinal mucosa. Its function is the oxidative deaminating of several polyamines, essential substances for cell proliferation. DAO is thus a regulating enzyme in rapidly proliferating tissues such a bone marrow and intestinal mucosa. Results from several studies have demonstrated that both ornithine decarboxylase (ODC) and DAO activity rise during adaptive hyperplasia seen after small bowel resection. The ODC-dependent increase in polyamine content and subsequent increase in cell proliferative activity is probably downregulated locally in the villus tip by the increased DAO activity. DAO is normally present in very small amounts in the circulation and its basal plasma levels are positively correlated with the maturity and integrity of the intestinal mucosa. After intravenous administration of heparin, DAO is released from its capillary binding sites in the lamina propria into the peripheral circulation. Measurement of postheparin DAO release enhances its sensitivity and is now extensively studied to assess its value as follow-up or screening test for several enteropathies. Measuring basal as well as postheparin DAO levels has potential relevance following small bowel transplantation. Rejection of the small bowel graft leads to mucosal damage, which could conceivably lead to changes in DAO activity.

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Polyamines, ribonucleases, and the stability of RNA

Cited by 32 publications

References 119 publications

Role of Polyamines in the Control of Cell Proliferation and Differentiation

Role of Polyamines in the Control of Cell Proliferation and Differentiation

A role for polyamines in glucose-stimulated insulin-gene expression

Diamine Oxidase: An Overview of Historical, Biochemical and Functional Aspects

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