PMID- 16133867
OWN - NLM
STAT- MEDLINE
DCOM- 20071206
LR  - 20191210
IS  - 1360-8185 (Print)
IS  - 1360-8185 (Linking)
VI  - 10
IP  - 4
DP  - 2005 Aug
TI  - Decreased apoptosis in polyamine depleted IEC-6 cells depends on Akt-mediated 
      NF-kappaB activation but not GSK3beta activity.
PG  - 759-76
AB  - The PI3-kinase/Akt pathway promotes cell survival in many different cell types 
      including intestinal epithelial cells. Increased AKT activation in polyamine 
      depleted intestinal epithelial cells correlated well with the decrease in 
      TNF-alpha-induced apoptosis. Increased Akt activation and GSK3beta (Ser 9) 
      phosphorylation without significant effect on Bad (Ser136) phosphorylation 
      indicate that Akt-mediated protection is independent of Bad phosphorylation but 
      may depend on GSK3beta. Pretreatment of polyamine-depleted cells with LY294002 
      increased caspase-9 and caspase-3 activation and decreased basal levels of 
      GSK-3beta phosphorylation. Inhibition of GSK3beta activity using AR-A014418 or 
      lithium chloride or siRNA-mediated downregulation of its expression had no effect 
      on apoptosis. Inhibition of PI3-kinase and over-expression of dominant negative 
      Akt (DN-AKT), significantly increased apoptosis in polyamine depleted cells. 
      DN-Akt expression reversed the protective effect of polyamine depletion on 
      apoptosis. DN-Akt, as well as the PI3-kinase inhibitors, prevented Akt activation 
      and subsequent translocation of NF-kappaB to the nucleus. Constitutively active 
      Akt (CA-AKT) expression increased resistance to TNF-alpha-induced apoptosis. 
      Constitutively active-Akt expression increased nuclear staining of NF-kappaB. 
      Moreover, polyamine depletion of DN-Akt cells prevented basal and 
      TNF-alpha-induced IkappaBalpha phosphorylation. Prevention of NF-kappaB 
      activation in DN-IkappaBalpha-transfected cells increased apoptosis in control 
      cells and restored it in polyamine-depleted cells to control levels. These data 
      indicate that Akt regulates the mitochondrial pathway, preventing activation of 
      caspase-9 and thereby caspase-3 via NF-kappaB and these effects are independent 
      of GSK-3beta activity.
FAU - Bhattacharya, S
AU  - Bhattacharya S
AD  - Department of Physiology, The University of Tennessee Health Science Center, 894 
      Union Ave., Memphis, Tennessee 38163, USA.
FAU - Ray, R M
AU  - Ray RM
FAU - Johnson, L R
AU  - Johnson LR
LA  - eng
GR  - DK-16505/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (Androstadienes)
RN  - 0 (Chromones)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Morpholines)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, rat)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Polyamines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-Associated Death Protein)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 17885-08-4 (Phosphoserine)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
RN  - XVA4O219QW (Wortmannin)
RN  - ZQN1G5V6SR (Eflornithine)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Caspase 3/metabolism
MH  - Caspase 9/metabolism
MH  - Cell Line
MH  - Cell Nucleus/drug effects/metabolism
MH  - Chromones/pharmacology
MH  - Eflornithine/pharmacology
MH  - Enzyme Activation/drug effects
MH  - Genes, Dominant
MH  - Glycogen Synthase Kinase 3/antagonists & inhibitors/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - I-kappa B Proteins/metabolism
MH  - Morpholines/pharmacology
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation/drug effects
MH  - Phosphoserine/metabolism
MH  - Polyamines/*metabolism
MH  - Protein Transport/drug effects
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Wortmannin
MH  - bcl-Associated Death Protein/metabolism
EDAT- 2005/09/01 09:00
MHDA- 2007/12/07 09:00
CRDT- 2005/09/01 09:00
PHST- 2005/09/01 09:00 [pubmed]
PHST- 2007/12/07 09:00 [medline]
PHST- 2005/09/01 09:00 [entrez]
AID - 10.1007/s10495-005-2943-3 [doi]
PST - ppublish
SO  - Apoptosis. 2005 Aug;10(4):759-76. doi: 10.1007/s10495-005-2943-3.