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

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Abstract

Although intracellular polyamine levels are highly regulated, it is unclear whether intracellular putrescine (PUT), spermidine (SPD), or spermine (SPM) levels act as a sensor to regulate their synthesis or uptake. Polyamines have been shown to induce AZ1 expression through a unique +1 frameshifting mechanism. However, under physiological conditions which particular polyamine induces AZ1, and thereby ODC activity, is unknown due to their inter-conversion. In this study we demonstrate that SPD regulates AZ1 expression under physiological conditions in IEC-6 cells. PUT and SPD showed potent induction of AZ1 within 4 h in serum-starved confluent cells grown in DMEM (control) medium. Unlike control cells, PUT failed to induce AZ1 in cells grown in DFMO containing medium; however, SPD caused a robust AZ1 induction in these cells. SPM showed very little effect on AZ1 expression in both the control and polyamine-depleted cells. Only SPD induced AZ1 when S-adenosylmethionine decarboxylase (SAMDC) and/or ODC were inhibited. Surprisingly, addition of DENSpm along with DFMO restored AZ1 induction by putrescine in polyamine-depleted cells suggesting that the increased SSAT activity in response to DENSpm converted SPM to SPD, leading to the expression of AZ1. This study shows that intracellular SPD levels controls AZ1 synthesis.

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Acknowledgments

This publication was made possible by Grants (Number DK-16505) from the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) and by support from the Thomas A. Gerwin endowment. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Health.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, University of Tennessee Health Science Center, 894 Union Avenue, Memphis, TN, 38163, USA

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

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  1. Ramesh M. Ray
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  2. Sujoy Bhattacharya
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  3. Mitul N. Bavaria
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  5. Leonard R. Johnson
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Correspondence to Ramesh M. Ray.

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Ray, R.M., Bhattacharya, S., Bavaria, M.N. et al. Spermidine, a sensor for antizyme 1 expression regulates intracellular polyamine homeostasis. Amino Acids 46, 2005–2013 (2014). https://doi.org/10.1007/s00726-014-1757-4

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  • DOI: https://doi.org/10.1007/s00726-014-1757-4

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