PMID- 23131565
OWN - NLM
STAT- MEDLINE
DCOM- 20130402
LR  - 20161125
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 429
IP  - 1-2
DP  - 2012 Dec 7
TI  - Transcriptional regulation of specific protein 1 (SP1) by hypoxia-inducible 
      factor 1 alpha (HIF-1alpha) leads to PRNP expression and neuroprotection from toxic 
      prion peptide.
PG  - 93-8
LID - S0006-291X(12)02078-5 [pii]
LID - 10.1016/j.bbrc.2012.10.086 [doi]
AB  - Our previous study demonstrated that hypoxia-inducible factor-1 (HIF-1)-mediated 
      neuroprotective effects are related to cellular prion protein (PrPc) gene (PRNP) 
      regulation under hypoxic conditions. However, the mechanism of HIF-1alpha-mediated 
      PRNP gene regulation in prion-mediated neurodegenerative disorders is not clear. 
      Transcription factor specific protein 1 (SP1) is necessary for PRNP transcription 
      initiation, and SP1 gene expression is regulated through HIF-1alpha activation under 
      hypoxic conditions. Thus, we hypothesized that HIF-1alpha-mediated neuroprotection is 
      related to the SP1 transcription pathway as a result of PRNP gene regulation. 
      Inhibition of SP1 expression blocked the HIF-1alpha-mediated protective effect 
      against prion-mediated neurotoxicity. Also, knockdown of HIF-1alpha induced 
      downregulation of SP1 expression and sensitivity to prion-mediated neurotoxicity, 
      whereas upregulation of SP1 transcriptional activity lead to protection against 
      prion-mediated neuron cell death and PRNP gene expression even in HIF-1alpha depleted 
      cells. This report is the first study demonstrating that HIF-1alpha-mediated SP1 
      expression regulates PrPc transcription, and upregulation of SP1 induced by 
      HIF-1alpha plays a key role in protection from prion-mediated neurotoxicity. These 
      studies suggest that transcription factor SP1 may be involved in the pathogenesis 
      of prion diseases and also may be a potential therapeutic option for 
      neurodegeneration caused by the pathological prion protein, PrPsc.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Jeong, Jae-Kyo
AU  - Jeong JK
AD  - Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National 
      University, Jeonju, Jeonbuk 561-756, South Korea.
FAU - Park, Sang-Youel
AU  - Park SY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121103
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (PRNP protein, human)
RN  - 0 (Peptide Fragments)
RN  - 0 (Prion Proteins)
RN  - 0 (Prions)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (prion protein (106-126))
SB  - IM
MH  - Apoptosis/drug effects
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Peptide Fragments/*pharmacology
MH  - Prion Diseases/genetics/metabolism
MH  - Prion Proteins
MH  - Prions/*genetics/*pharmacology
MH  - Signal Transduction
MH  - Sp1 Transcription Factor/*genetics
MH  - *Transcription, Genetic
EDAT- 2012/11/08 06:00
MHDA- 2013/04/03 06:00
CRDT- 2012/11/08 06:00
PHST- 2012/10/20 00:00 [received]
PHST- 2012/10/25 00:00 [accepted]
PHST- 2012/11/08 06:00 [entrez]
PHST- 2012/11/08 06:00 [pubmed]
PHST- 2013/04/03 06:00 [medline]
AID - S0006-291X(12)02078-5 [pii]
AID - 10.1016/j.bbrc.2012.10.086 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Dec 7;429(1-2):93-8. doi: 
      10.1016/j.bbrc.2012.10.086. Epub 2012 Nov 3.