PMID- 20713124
OWN - NLM
STAT- MEDLINE
DCOM- 20110512
LR  - 20220812
IS  - 1638-6183 (Electronic)
IS  - 0300-9084 (Linking)
VI  - 92
IP  - 12
DP  - 2010 Dec
TI  - Modulation of hypoxia-inducible factor-1alpha expression by mitochondrial 
      NADP+-dependent isocitrate dehydrogenase.
PG  - 1908-13
LID - 10.1016/j.biochi.2010.08.004 [doi]
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) is an important 
      regulator of the tumor response to hypoxia, including increased angiogenesis, 
      glycolytic metabolism, and resistance to apoptosis. In the current study, small 
      interfering RNA (siRNA)-mediated knockdown of mitochondrial NADP(+)-dependent 
      isocitrate dehydrogenase (IDPm) suppressed hypoxia-induced stimulation of HIF-1alpha 
      protein expression in PC3 human prostate cancer cells. Treatment with the 26S 
      proteasome inhibitor MG132 failed to abrogate the suppression of HIF-1alpha 
      accumulation induced by IDPm knockdown, whereas HIF-1alpha levels were reduced by 
      cycloheximide treatment in both control and IDPm siRNA-transfected cells. These 
      results suggested that the suppression of HIF-1alpha accumulation by IDPm knockdown 
      in PC3 cells was due to an inhibition of HIF-1alpha transcription. Inactivation of 
      the phosphoinsotide-3 kinase (PI3K)/Akt pathway decreased HIF-1alpha expression 
      through inactivation of Sp1. Thus, IDPm siRNA functioned as a potentially useful 
      agent for targeting chemo- and radio-resistant hypoxic cells within solid tumors 
      through inhibition of HIF-1alpha expression.
CI  - Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.
FAU - Kim, Sung Youl
AU  - Kim SY
AD  - School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook 
      National University, Taegu 702-701, Republic of Korea.
FAU - Park, Jeen-Woo
AU  - Park JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100814
PL  - France
TA  - Biochimie
JT  - Biochimie
JID - 1264604
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Leupeptins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Sp1 Transcription Factor)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 1.1.1.41 (IDH2 protein, human)
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 1.1.1.42 (isocitrate dehydrogenase (NADP+))
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Cell Line, Tumor
MH  - Cycloheximide/pharmacology
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Free Radical Scavengers/pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Immunoblotting
MH  - Isocitrate Dehydrogenase/genetics/*metabolism
MH  - Leupeptins/pharmacology
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA Interference
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Sp1 Transcription Factor/metabolism
EDAT- 2010/08/18 06:00
MHDA- 2011/05/13 06:00
CRDT- 2010/08/18 06:00
PHST- 2010/03/17 00:00 [received]
PHST- 2010/07/14 00:00 [revised]
PHST- 2010/08/03 00:00 [accepted]
PHST- 2010/08/18 06:00 [entrez]
PHST- 2010/08/18 06:00 [pubmed]
PHST- 2011/05/13 06:00 [medline]
AID - S0300-9084(10)00287-7 [pii]
AID - 10.1016/j.biochi.2010.08.004 [doi]
PST - ppublish
SO  - Biochimie. 2010 Dec;92(12):1908-13. doi: 10.1016/j.biochi.2010.08.004. Epub 2010 
      Aug 14.