ArticleThe Biochemical journal1994
Inhibition of immediate-early-gene induction in renal mesangial cells by depletion of intracellular polyamines.
Article in The Biochemical journal, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed, 7 citations in OpenAlex.
- Polyamine metabolism is sensitive to glycolysis inhibition in human neuroblastoma cells.The Journal of biological chemistry · 2015Article
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5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitogens have been shown to stimulate the activity of the rate-limiting enzyme for polyamine synthesis, ornithine decarboxylase (ODC), and ODC mRNA expression in cultured rat mesangial cells (MCs). In addition, inhibition of ODC by alpha-difluoromethylornithine (DFMO) results in growth arrest of MCs. To elucidate the mechanisms involved in the inhibition of MC proliferation due to polyamine depletion, we studied the effects of DFMO on the activation of phospholipase C and induction of the immediate early genes (IEGs), c-fos, c-jun and Egr-1, which are thought to regulate cell growth. Mitogenic 10% fetal-calf serum (FCS) and 1 unit/ml thrombin activated phospholipase C in MCs within 30 s, as assessed by generation of [3H]inositol phosphates. This activation was not affected by DFMO. mRNAs of the IEGs c-fos, c-jun and Egr-1 were induced by FCS within 15 min. Expression of these genes reached a peak at 60 min and disappeared at 3 h. Treatment of MCs with a growth-suppressing dose of DFMO (5 mM) inhibited mRNAs of all three IEGs by 52-87% at 1 h. Total expression of Egr-1 over 20-120 min was diminished by 41%, and the time point of maximal expression was delayed by 40 min. This inhibitory effect was abolished in a time-dependent manner (1-3 days) by prior addition of 200 microM putrescine, the reaction product of ODC. Egr-1 mRNA expression was super-induced by the inhibitor of protein synthesis, cycloheximide. This effect was also blocked by DFMO. The results indicate that the DFMO-induced process of MC growth inhibition involves steps necessary for IEG activation. The signal-transduction step sensitive to polyamines occurs distal to the activation of phospholipase C. Since reconstitution of normal induction of IEGs requires 3 days, it seems likely that polyamine depletion affects the regulation of IEG expression in an indirect fashion. We conclude that activation of IEGs requires the presence of polyamines and plays a significant role in the induction of MC replication.
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