Recent advances in the biochemistry of polyamines in eukaryotes

Pegg, Anthony E.

doi:10.1042/bj2340249

Cited by 1,545 publications

(819 citation statements)

References 145 publications

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“…In contrast to polyamines, 5'-deoxy-5'-methylthioadenosine, a metabolite formed in stoichiometric amounts with spermidine and spermine during the aminopropyl transfer steps, was found to be a good competitive inhibitor of the Ptdlns kinase of human polymorphonuclear leukocytes (Pike & DeMeester, 1988). This observation, however, might not be relevant to cellular conditions, since in most systems this nucleoside is rapidly cleaved by a phosphorylase (Pegg, 1986 (Nishizuka, 1984(Nishizuka, . 1986) has emerged; the intracellular distribution of this important enzyme can fluctuate rapidly between a soluble (inactive with most substrates) form, and a membrane-bound form (active).…”

Section: Polyamines and Transportmentioning

confidence: 99%

“…Their roles in the regulation of major functions in cell growth, cell differentiation and their intricate and exquisitely regulated biosynthetic pathways have attracted considerable attention during the last few decades. Authoritative reviews and books have dealt with these aspects, including the design of enzyme inhibitors which by depleting cells of their normal polyamine contents provoke cell growth arrest and other pharmacologically important phenomena (see, e.g., Heby, 1981;Pegg & McCann, 1982;Tabor & Tabor, 1984;Pegg, 1986Pegg, , 1988McCann, e al., 1987). Although the functions attributed to the polyamines are numerous, their modes of action at a molecular level remain a matter of speculation.…”

Section: Introductionmentioning

confidence: 99%

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Influence of polyamines on membrane functions

Schuber

1989

Biochemical Journal

421

222

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Section: Polyamines and Transportmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of polyamines on membrane functions

Schuber

1989

Biochemical Journal

421

222

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“…ODC is the rate-limiting enzyme in the biosynthesis of mammalian polyamines. Polyamine metabolism plays a decisive role in nucleic acid synthesis, cell proliferation and di erentiation, as well as malignant transformation (Pegg, 1986). However, TPA-induced events upstream of ODC activation are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Tumor promoter-induced ornithine decarboxylase gene expression occurs independently of AP-1 activation

1999

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Activator protein 1 (AP-1) transactivation and ornithine decarboxylase (ODC) activity have been established as essential downstream e ectors of mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). Previous studies have shown that inhibition of either AP-1 transactivation or ODC activity suppressed tumor promoter-induced transformation. By utilizing the JB6 mouse epidermal cell system, the present study determined whether TPA-induced ODC gene expression and activity is independent of AP-1 transactivation. In three independent JB6 (P + ) clones, stably expressing dominant negative c-jun, TPA-induced ODC gene expression and activity were similar compared to JB6 P + cells expressing vector-control alone, while AP-1-dependent transcription was inhibited. Transformationinsensitive JB6 (P 7 ) cells, which lack TPA-inducible cjun expression, also exhibited similar induction of ODC activity by TPA. a-Di¯uoromethylornithine, an irreversible inhibitor of ODC, attenuated, at an equivalent IC 50 , both TPA-induced ODC activity and anchorage-independent growth of JB6 P + cells, despite no inhibition of AP-1 transactivation. Taken together, the results presented indicate that TPA-induced ODC gene expression and activity are independent of AP-1 transactivation. Because inhibition of either AP-1 or ODC precludes TPA-induced transformation, and because ODC is independent of AP-1, we propose that there are at least two pathways to transformation. Each pathway is required but not su cient for transformation.

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“…ODC is the first and rate-limiting enzyme in the polyamine pathway and, therefore, it is a key regulatory enzyme in growth processes (Pegg, 1986). The enzyme function is to convert ornithine to putrescine, and changes in ODC activity reflect the rate of macromolecular synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…One of them is ornithine decarboxylase (odc) gene encoding a key regulatory enzyme in the biosynthesis of polyamines that are essential for cell proliferation (Pegg, 1986). ODC and polyamines can also act as facilitating factors in triggering apoptosis (Tiberio et al, 2001).…”

mentioning

confidence: 99%

Do altering in ornithine decarboxylase activity and gene expression contribute to antiproliferative properties of COX inhibitors?

et al. 2003

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Two isoforms of cyclooxygenase (COX) participate in growth control; COX-1 is constitutively expressed in most cells, and COX-2 is an inducible enzyme in response to cellular stimuli. An induction of COX-2 found in neoplastic tissues results in increased cell growth, inhibition of apoptosis, activation of angiogenesis, and decreased immune responsiveness. Although both COX-1 and COX-2 inhibitors are suppressors of cell proliferation and appear to be chemopreventive agents for tumorigenesis, the molecular mechanisms mediating antiproliferative effect of COX inhibitors are still not well defined. This study contrasts and compares the effects of aspirin and celecoxib, inhibitors of COX-1 and COX-2, in rat hepatoma HTC-IR cells. The following were assessed: cell proliferation and apoptosis, ornithine decarboxylase (ODC) activity, and pattern expression of three immediate-early genes, c-myc, Egr-1, and c-fos. We have shown that the treatment of hepatocytes in vitro with the selective COX-2 inhibitor, celecoxib, was associated with induction of apoptosis and complete inhibition of cellular proliferation. Aspirin exhibited a small antiproliferative effect that was not associated with apoptosis. Treatment with celecoxib produced dose-and time-dependent decrease in ODC activity. In addition, at higher drug concentration the decrease in ODC activity was greater in proliferating than in resting cells. Much lesser inhibitory effect on ODC activity was observed in aspirin-treated cells. The two COX inhibitors did not change c-myc expression, significantly decreased the expression of Egr-1, and differentially altered expression of c-fos; aspirin did not change, but celecoxib dramatically decreased the levels of c-fos-mRNA. Our study revealed that celecoxib and aspirin share the ability to inhibit ODC activity and alter the pattern of immediate-early gene expression. It seems that some of the observed effects are likely to be related to COX-independent pathways. The precise mechanisms of action of COX inhibitors should be defined before using these drugs for cancer chemopreventive therapy.

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Recent advances in the biochemistry of polyamines in eukaryotes

Cited by 1,545 publications

References 145 publications

Influence of polyamines on membrane functions

Influence of polyamines on membrane functions

Tumor promoter-induced ornithine decarboxylase gene expression occurs independently of AP-1 activation

Do altering in ornithine decarboxylase activity and gene expression contribute to antiproliferative properties of COX inhibitors?

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