PMID- 24930035
OWN - NLM
STAT- MEDLINE
DCOM- 20150828
LR  - 20211021
IS  - 1438-2199 (Electronic)
IS  - 0939-4451 (Print)
IS  - 0939-4451 (Linking)
VI  - 46
IP  - 9
DP  - 2014 Sep
TI  - Antizyme (AZ) regulates intestinal cell growth independent of polyamines.
PG  - 2231-9
LID - 10.1007/s00726-014-1777-0 [doi]
AB  - 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 microM 
      spermidine (SPD), DFMO + 5 microM spermine (SPM), or DFMO + 10 microM 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.
FAU - Ray, Ramesh M
AU  - Ray RM
AD  - Department of Physiology, University of Tennessee Health Science Center, 894 
      Union Avenue, Memphis, TN, 38163, USA, rray3@uthsc.edu.
FAU - Bhattacharya, Sujoy
AU  - Bhattacharya S
FAU - Bavaria, Mitul N
AU  - Bavaria MN
FAU - Viar, Mary Jane
AU  - Viar MJ
FAU - Johnson, Leonard R
AU  - Johnson LR
LA  - eng
GR  - R01 DK016505/DK/NIDDK NIH HHS/United States
GR  - R37 DK016505/DK/NIDDK NIH HHS/United States
GR  - DK-16505/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140615
PL  - Austria
TA  - Amino Acids
JT  - Amino acids
JID - 9200312
RN  - 0 (Biogenic Polyamines)
RN  - 0 (Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (ornithine decarboxylase antizyme)
SB  - IM
MH  - Biogenic Polyamines/*pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Epithelial Cells/cytology/*metabolism
MH  - Humans
MH  - Intestinal Mucosa/cytology/*metabolism
MH  - Proteins/genetics/*metabolism
MH  - RNA, Small Interfering/genetics/metabolism
PMC - PMC4134379
MID - NIHMS605458
EDAT- 2014/06/16 06:00
MHDA- 2015/09/01 06:00
PMCR- 2015/09/01
CRDT- 2014/06/16 06:00
PHST- 2014/04/04 00:00 [received]
PHST- 2014/06/04 00:00 [accepted]
PHST- 2014/06/16 06:00 [entrez]
PHST- 2014/06/16 06:00 [pubmed]
PHST- 2015/09/01 06:00 [medline]
PHST- 2015/09/01 00:00 [pmc-release]
AID - 10.1007/s00726-014-1777-0 [doi]
PST - ppublish
SO  - Amino Acids. 2014 Sep;46(9):2231-9. doi: 10.1007/s00726-014-1777-0. Epub 2014 Jun 
      15.