Antizyme (AZ) regulates intestinal cell growth independent of polyamines

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 5 mM difluoromethylornithine (DFMO) to inhibit ODC, DFMO + 5 μM spermidine (SPD), DFMO + 5 μM 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.

Original languageEnglish (US)
Pages (from-to)2231-2239
Number of pages9
JournalAmino Acids
Volume46
Issue number9
DOIs
StatePublished - 2014

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Eflornithine
Polyamines
Cell growth
Growth
Spermidine
Putrescine
Spermine
Asparagine
Level control
Cell proliferation
Small Interfering RNA
Cell Count
Epithelial Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry
  • Medicine(all)

Cite this

Antizyme (AZ) regulates intestinal cell growth independent of polyamines. / Ray, Ramesh M.; Bhattacharya, Sujoy; Bavaria, Mitul N.; Viar, Mary Jane; Johnson, Leonard R.

In: Amino Acids, Vol. 46, No. 9, 2014, p. 2231-2239.

Research output: Contribution to journalArticle

Ray, Ramesh M. ; Bhattacharya, Sujoy ; Bavaria, Mitul N. ; Viar, Mary Jane ; Johnson, Leonard R. / Antizyme (AZ) regulates intestinal cell growth independent of polyamines. In: Amino Acids. 2014 ; Vol. 46, No. 9. pp. 2231-2239.
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