Cultured hepatoma cells for the study of enzyme regulation: Induction of ornithine decarboxylase by insulin and asparagine

Potter, R. Van; Evanson, T.; Gayda, Debra P.; Gurr, James A.

doi:10.1007/bf02618878

Cited by 12 publications

(5 citation statements)

References 26 publications

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“…Ornithine decarboxylase activity can be induced by all known classes of hormones acting on their target tissues (1,4), and its induction is generally associated with the initiation of cell growth. Nerve growth factor (5) (NGF), epidermal growth factor (6) (EGF), and insulin have been shown to induce ornithine decarboxylase activity in various responsive cell lines, and it has been generally assumed that these hormones induce ornithine decarboxylase activity directly (7)(8)(9)(10)(11)(12). We present evidence that the induction of ornithine decarboxylase by these hormones and, therefore, the subsequent ornithine decarboxylase dependent cell growth is mediated by specific amino acids.…”

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confidence: 90%

“…Amino acids are not required for the induction of all enzymes; for instance, in one well-studied case, it was shown that the induction of tyrosine amino-transferase by dexamethasone does not require amino acids (20). An interesting study on the regulation of ornithine decarboxylase activity by insulin and by asparagine in KRC-7 hepatoma cells also has been reported recently (12).…”

mentioning

confidence: 98%

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Induction of ornithine decarboxylase activity by insulin and growth factors is mediated by amino acids.

Rinehart¹,

Canellakis²

1985

Proc. Natl. Acad. Sci. U.S.A.

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The polypeptide growth factors, nerve growth factor, epidermal growth factor, and platelet-derived growth factor, as well as insulin do not induce ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) unless a minimal concentration of an ornithine decarboxylase-inducing amino acid, such as asparagine, is present in the medium. The effects of the growth factors were studied in appropriately responsive cell lines: pheochromocytoma (PC12) cells for nerve and epidermal growth factors, fibroblasts (NIH 3T3) for platelet-derived growth factor, and fibroblasts and hepatoma (KRC-7) cells for insulin. The nonmetabolizable amino acid analog alpha-aminoisobutyric acid can replace asparagine, indicating that the covalent modification of the inducing amino acid is not necessary for the induction of ornithine decarboxylase by these growth factors. For the same intracellular concentration of the inducing amino acid, the presence of the growth factors induces higher levels of ornithine decarboxylase. The evidence indicates that these growth factors do not induce ornithine decarboxylase by raising the intracellular concentration of amino acids but rather act synergistically with the inducing amino acid. Evidence is provided that the induction of polyamine-dependent growth by these growth factors is mediated by amino acids. The relationship of these results to the A and N amino acid transport systems and to the Na+ influxes in relation to growth is discussed.

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confidence: 90%

mentioning

confidence: 98%

Induction of ornithine decarboxylase activity by insulin and growth factors is mediated by amino acids.

Rinehart¹,

Canellakis²

1985

Proc. Natl. Acad. Sci. U.S.A.

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“…These cells express receptors that bind insulin with a similar affinity to isolated rat hepatocytes and adipocytes, and insulin induces glycogen synthesis at physiologic concentrations (16). Further, as in the liver, in these cell lines insulin regulates the transcription, mRNA levels, and activity of gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and ornithine decarboxylase (17)(18)(19)(20)(21)(22)(23)(24).…”

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confidence: 99%

Insulin Signal Transduction Pathways and Insulin-induced Gene Expression

Keeton

Amsler

Venable

et al. 2002

Journal of Biological Chemistry

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Insulin regulates metabolic activity, gene transcription, and cell growth by modulating the activity of several intracellular signaling pathways. Insulin activation of one mitogen-activated protein kinase cascade, the MEK/ERK kinase cascade, is well described. However, the effect of insulin on the parallel p38 pathway is less well understood. The present work examines the effect of inhibiting the p38 signaling pathway by use of specific inhibitors, either alone or in combination with insulin, on the activation of ERK1/2 and on the regulation of gene transcription in rat hepatoma cells. Activation of ERK1/2 was induced by insulin and was dependent on the activation of MEK1, the kinase upstream of ERK in this pathway. Treatment of cells with p38 inhibitors also induced ERK1/2 activation/phosphorylation. The addition of p38 inhibitors followed by insulin addition resulted in a greater than additive activation of ERK1/2. The two genes studied, c-Fos and Pip92, are immediateearly genes that are dependent on the ERK1/2 pathway for insulin-regulated induction because the insulin effect was inhibited by pretreatment with a MEK1 inhibitor. The addition of p38 inhibitors induced transcription of both genes in a dose-dependent manner, and insulin stimulation of both genes was enhanced by prior treatment with p38 inhibitors. The ability of the p38 inhibitors to induce ERK1/2 and gene transcription, both alone and in combination with insulin, was abolished by prior inhibition of MEK1. These data suggest possible cross-talk between the p38 and ERK1/2 signaling pathways and a potential role of p38 in insulin signaling.

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“…Several studies have shown that exposure to drugs of abuse (43,44) alters embryonic trophic factor (mitogen) levels and also lowers tissue responsiveness to these factors. While, several trophic factors modulate ODC activity (44)(45)(46)(47)(48)(49)(50)(51), we choose to study the effects of cocaine on the response of chick cells to insulin, a potent tyrosine kinase-linked mitogenic factor. The data shown in Figure 4 indicate that in this model, cocaine exposure blocks the rapid increase in cell division induced by insulin exposure.…”

Section: Discussionmentioning

confidence: 99%

Embryonic Growth Inhibition Induced by Cocaine Is Associated with the Suppression of Ornithine Decarboxylase Activity

Sandstrom

Pennington

1993

Experimental Biology and Medicine

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Cocaine use during pregnancy results in significant increases in fetal morbidity and mortality. Multiple maternal and environmental variables influence the fetal response to cocaine, and growth suppression of the developing child is frequently associated with in utero cocaine exposure. Using intact chick embryos as well as cultured embryonic tissue as a model, we report that the growth suppression induced by cocaine exposure is correlated with molecular changes occurring directly in the embryonic cells and that these molecular changes appear to be distinct from other maternal, placental, or environmental effects of the drug, including anoxia. Specifically, embryonic cocaine exposure suppresses the normal developmental increase in ornithine decarboxylase (ODC) enzymatic activity. The loss of ODC activity during the early stages of development is dose dependent and is correlated with the degree of growth suppression. The cocaine-induced loss of decarboxylase activity is specific to ODC, but cocaine, per se, has no effect on ODC activity in vitro. Moreover, a single dose of exogenous putrescine given at 120 hr of incubation blocks the cocaine-induced growth suppression. In cultured embryonic tissue, cocaine exposure inhibits the ability of a known trophic factor (insulin) to induce growth and also blocks the associated increase in ODC activity. Preliminary data suggest that cocaine hinders the binding of insulin to embryonic cells. Because ODC is a focal enzyme for the regulation of growth, the data suggest that cocaine-induced changes in the mitogenic induction of embryonic/fetal ODC activity may be a part of the biochemical mechanism by which cocaine-induced growth inhibition occurs.

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Cultured hepatoma cells for the study of enzyme regulation: Induction of ornithine decarboxylase by insulin and asparagine

Cited by 12 publications

References 26 publications

Induction of ornithine decarboxylase activity by insulin and growth factors is mediated by amino acids.

Induction of ornithine decarboxylase activity by insulin and growth factors is mediated by amino acids.

Insulin Signal Transduction Pathways and Insulin-induced Gene Expression

Embryonic Growth Inhibition Induced by Cocaine Is Associated with the Suppression of Ornithine Decarboxylase Activity

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