Spermidine, a sensor for antizyme 1 expression regulates intracellular polyamine homeostasis

Ray, Ramesh M.; Bhattacharya, Sujoy; Bavaria, Mitul; Viar, Mary Jane; Johnson, Leonard R.

doi:10.1007/s00726-014-1757-4

Cited by 14 publications

(18 citation statements)

References 52 publications

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“…This induction could be explained by a post-translational regulation mechanism of ODC in which Homspd would be involved (Pegg 2006). In that sense, Spd has been regarded as the most potent feedback inhibitor of ODC by forming a complex with this enzyme (Ray et al 2014). Under salt stress conditions, the response of ODC was different depending on the strain with a strong induction in the Wt that would be behind the Spd and Spm accumulation in this strain and an inhibition in the HSS− that would justify the PA decline by the salinity (Fig.…”

Section: Discussionmentioning

confidence: 97%

Homospermidine synthase contributes to salt tolerance in free-living Rhizobium tropici and in symbiosis with Phaseolus vulgaris

et al. 2016

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Background and aims Homospermidine is known to be the most abundant polyamine in root nodules of Phaseolus vulgaris induced by Rhizobium tropici. In addition, homospermidine is involved in the stress tolerance of fast-growing rhizobia and in the bacteroid protection from environmental changes. For that reason, in this work, we have investigated the role of the rhizobial homospermidine synthase in the response of P. vulgaris root nodules to salinity. Materials and methods A mutant strain of R. tropici impaired in the synthesis of homospermidine has been constructed (Rt hss::Ω, Sp r ) and the response to salinity of the free-living and symbiotic bacteria has been analyzed. Plants of P. vulgaris inoculated with the mutant strain were treated with 100 mM NaCl, and the concentration of polyamines was determined in different nodular fractions together with nitrogen fixation and gene expression of polyamine biosynthetic enzymes.Results Neither homospermidine nor 4-aminobutilcadaverine was detected in the free-living mutant bacteria and in nodules of plants inoculated with Rt hss::Ω, Sp r . This strain was more sensitive to salinity than the wild type, and plants inoculated with the mutant bacteria had lower nodule fresh weight than with the wild type. Conclusion Homospermidine synthase contributes to salt stress in both free-living and symbiotic bacteria. Despite the synthesis of homospermidine, this enzyme produces also 4-aminobutilcadaverine. Based on the lower nodule fresh weight and plant biomass reduction induced by salinity in plants inoculated with the mutant strain, this enzyme seems to be involved in nodule organogenesis and salt tolerance.

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Section: Discussionmentioning

confidence: 97%

Homospermidine synthase contributes to salt tolerance in free-living Rhizobium tropici and in symbiosis with Phaseolus vulgaris

et al. 2016

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“…We have recently shown that spermidine is the only polyamine that directly stimulates AZ synthesis (Ray et al 2014). In that study blocking the conversion of putrescine to spermidine by inhibiting S-adenosylmethionine decarboxylase (SAMDC), eliminated the increase in AZ levels caused by the diamine.…”

Section: Discussionmentioning

confidence: 99%

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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“…Furthermore, amino acids like GLN and ASN inhibited, while LYS, VAL, and ORN increased AZ in EBSS. Recently we have established that among the three polyamines, spermidine is a direct and physiological regulator of AZ synthesis (23). …”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, polyamines were absolutely required for the induction of AZ both in the presence and absence of amino acids (23). In the current study, we determined the role of mTORC1, mTORC2 and polyamines in AZ synthesis.…”

Section: Introductionmentioning

confidence: 99%

Interaction of polyamines and mTOR signaling in the synthesis of antizyme (AZ)

Ray

Bavaria

Johnson

2015

Cellular Signalling

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Tissue polyamine levels are largely determined by the activity of ornithine decarboxylase (ODC, EC 4.1.17), which catalyzes the conversion of ornithine to the diamine putrescine. The activity of the enzyme is primarily regulated by a negative feedback mechanism involving ODC antizyme (AZ). Our previous studies demonstrated that AZ synthesis is stimulated by the absence of amino acids, the levels of which are sensed by the mTOR complex containing TORC1, which is stimulated by amino acids and inhibited by their absence, and TORC2 the function of which is not well defined. Polyamines, which cause a +1 ribosomal frameshift during the translation of AZ mRNA are required to increase AZ synthesis in both the presence and absence of amino acids. Amino acid starvation increases TORC2 activity. We have demonstrated that mTORC2 activity is necessary for AZ synthesis in the absence of amino acids. Tuberous sclerosis protein (TSC), a negative regulator of mTOR function regulates the activities of both the TORC1 and TORC2. TSC2 knockdown increased mTORC1 activity with concomitant inhibition of mTORC2 activity eliminating AZ induction in the absence of amino acids as well as that induced by spermidine. Thus, these results clearly demonstrate that in addition to polyamines, mTORC2 activity is necessary for AZ synthesis. Moreover, our results support a role for mTORC2 in the synthesis of a specific protein, AZ, which regulates growth of intestinal epithelial cells.

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Spermidine, a sensor for antizyme 1 expression regulates intracellular polyamine homeostasis

Cited by 14 publications

References 52 publications

Homospermidine synthase contributes to salt tolerance in free-living Rhizobium tropici and in symbiosis with Phaseolus vulgaris

Homospermidine synthase contributes to salt tolerance in free-living Rhizobium tropici and in symbiosis with Phaseolus vulgaris

Antizyme (AZ) regulates intestinal cell growth independent of polyamines

Interaction of polyamines and mTOR signaling in the synthesis of antizyme (AZ)

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