Amino Acids Regulate Expression of Antizyme-1 to Modulate Ornithine Decarboxylase Activity

Ray, Ramesh M.; Viar, Mary Jane; Johnson, Leonard R.

doi:10.1074/jbc.m111.232561

Cited by 21 publications

(34 citation statements)

References 63 publications

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“…1, 3 and 4, spermidine dramatically increased the synthesis of AZ and inhibited cell growth. Since ASN inhibits AZ synthesis (Ray et al 2012), we reasoned that the amino acid might restore the growth of cell cultures incubated with spermidine. Phase contrast micrographs in Fig.…”

Section: Resultsmentioning

confidence: 99%

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Antizyme (AZ) regulates intestinal cell growth independent of polyamines

et al. 2014

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Since antizyme (AZ) is known to inhibit cell proliferation and to increase apoptosis, the question arises as to whether these effects occur independently of polyamines. Intestinal epithelial cells (IEC-6) were grown in control medium and medium containing 5mM difluoromethylornithine (DFMO) to inhibit ODC, DFMO + 5μM spermidine (SPD), DFMO+ 5μM spermine (SPM), or DFMO+ 10 μM putrescine (PUT) for 4 days and various parameters of growth were measured along with AZ levels. Cell counts were significantly decreased and mean doubling times were significantly increased by DFMO. Putrescine restored growth in the presence of DFMO. However, both SPD and SPM when added with DFMO caused a much greater inhibition of growth than did DFMO alone, and both of these polyamines caused a dramatic increase in AZ. The addition of SPD or SPM to media containing DFMO + PUT significantly inhibited growth and caused a significant increase in AZ. IEC-6 cells transfected with AZ-siRNA grew more than twice as rapidly as either control cells or those incubated with DFMO, indicating that removal of AZ increases growth in cells in which polyamine synthesis is inhibited as well as in control cells. In a separate experiment the addition of SPD increased AZ levels and inhibited growth of cells incubated with DFMO by 50%. The addition of 10 mM asparagine (ASN) prevented the increase in AZ and restored growth to control levels. These results show that cell growth in the presence or absence of ODC activity and in the presence or absence of polyamines depends only on the levels of AZ. Therefore, the effects of AZ on cell growth are independent of polyamines.

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Section: Resultsmentioning

confidence: 99%

“…Their inhibition of AZ synthesis and its subsequent decrease then permit additional stimulation of ODC activity by other proliferating agents. In the absence of amino acids, for example, AZ synthesis increases rapidly for up to 6h, and this increase is essentially prevented by ASN (Ray et al 2012). …”

Section: Introductionmentioning

confidence: 99%

Antizyme (AZ) regulates intestinal cell growth independent of polyamines

et al. 2014

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“…The reason why Put levels are increased in both Kelly and SK-N-SH cells when treated with BPTES remains to be studied. However, because BPTES prevents glutamine from being used as an anaplerotic source for the tricarboxylic acid cycle through glutaminase, free glutamine could be the cause of this increment of Put due to the fact that amino acids, including glutamine, have been described to activate ODC through the mTOR-dependent regulation of antizyme synthesis (46).…”

Section: Discussionmentioning

confidence: 99%

Polyamine Metabolism Is Sensitive to Glycolysis Inhibition in Human Neuroblastoma Cells

Ruiz-Pérez

Medina

Urdiales

et al. 2015

Journal of Biological Chemistry

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Background: Polyamine metabolism is relevant in neuroblastoma progression. Results: Polyamine synthesis is hampered by glycolysis inhibition in neuroblastoma cells. Conclusion: Glycolysis inhibition triggers signaling events leading to decrease of N-Myc and ODC levels, resulting in decreased polyamine synthesis. Significance: Combined therapies targeting glucose metabolism and polyamine synthesis could be effective in the treatment of n-myc-expressing tumors.

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“…This leads us to the conclusion that TOR negatively regulates antizyme levels and that TOR inhibition induces antizyme expression independent of the cellular polyamine biosynthesis. In this context, it is interesting to note that recent findings in cell culture experiments have shown the amino acids asparagine and glutamine to regulate rat antizyme1 expression by differential activation of mammalian TORC-1 and TORC-2 (53,54). Here it was shown that amino acid starvation leads to inhibition of TORC-1 signaling, whereas TORC-2 is activated.…”

Section: Antizyme Expression Is Induced By Lack Of Nutrition and Regumentioning

confidence: 81%

Polyamine-independent Expression of Caenorhabditis elegans Antizyme

Stegehake

Kurosinski

Schürmann

et al. 2015

Journal of Biological Chemistry

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Background: Ornithine decarboxylase degradation by the proteasome is promoted by antizyme. Results: A novel reporter gene approach was established to monitor translational frameshifting of C. elegans antizyme in vivo. Conclusion: Induction of antizyme-frameshifting also occurs under stressful conditions, even in the absence of polyamine synthesis and independent of polyamine concentrations. Significance: A polyamine-independent regulation of frameshifting under stressful conditions is proposed.

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Amino Acids Regulate Expression of Antizyme-1 to Modulate Ornithine Decarboxylase Activity

Cited by 21 publications

References 63 publications

Antizyme (AZ) regulates intestinal cell growth independent of polyamines

Antizyme (AZ) regulates intestinal cell growth independent of polyamines

Polyamine Metabolism Is Sensitive to Glycolysis Inhibition in Human Neuroblastoma Cells

Polyamine-independent Expression of Caenorhabditis elegans Antizyme

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