PMID- 20153315
OWN - NLM
STAT- MEDLINE
DCOM- 20100622
LR  - 20151119
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 633
IP  - 1-3
DP  - 2010 May 10
TI  - Preconditioning protects against oxidative injury involving hypoxia-inducible 
      factor-1 and vascular endothelial growth factor in cultured astrocytes.
PG  - 24-32
LID - 10.1016/j.ejphar.2010.02.008 [doi]
AB  - Tolerance to brain injury involves hypoxia-inducible factor-1 (HIF-1) and its 
      target genes as the key pathway mediating a cascade of events including cell 
      survival, energetics, and angiogenesis. In this study, we established the 
      treatment paradigms for an in vitro model of tolerance to oxidative injury in 
      primary astrocytic cultures and further examined the roles for the HIF-1 
      signalling cascade. Isolated murine astrocytes were preconditioned with sub-toxic 
      concentrations of HIF-1 inducers and subsequently exposed to a H(2)O(2) insult, 
      where changes in cell viability and protein expression were determined. 
      Preconditioning with non-damaging concentrations of desferrioxamine (DFO) and 
      ethyl-3,4-dihydroxybenzoate (EDHB) significantly improved cellular viability 
      after H(2)O(2) injury treatment. Time course studies revealed that DFO and EDHB 
      treatments alone induced sequential activation of HIF-1 signal transduction where 
      nuclear HIF-1alpha protein accumulation was detected as early as 2h, followed by 
      downstream upregulation of intracellular and released VEGF from 4h and 8h 
      onwards, respectively. The protective effects of DFO and EDHB preconditioning 
      against H(2)O(2) injury were abolished by co-treatment with cycloheximide, an 
      inhibitor of protein synthesis. Importantly, when the anti-HIF-1 compound, 
      3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) was used, the 
      cytoprotection and VEGF accumulation produced by DFO and EDHB preconditioning 
      were diminished. These results indicate the essential role of the HIF-1 pathway 
      in our model of tolerance against oxidative injury in cultured astrocytes, and 
      suggest roles for astrocytic HIF-1 expression and VEGF release which may 
      influence the function of surrounding cells and vasculature during oxidative 
      stress-related brain diseases.
CI  - Copyright 2010 Elsevier B.V. All rights reserved.
FAU - Chu, Percy W Y
AU  - Chu PW
AD  - Molecular Neuropharmacology, Florey Neuroscience Institutes, University of 
      Melbourne, VIC 3010, Australia.
FAU - Beart, Philip M
AU  - Beart PM
FAU - Jones, Nicole M
AU  - Jones NM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100211
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hydroxybenzoates)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Indazoles)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 154453-18-6 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole)
RN  - 4YGJ96WTBG (ethyl protocatechuate)
RN  - 98600C0908 (Cycloheximide)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Cell Survival/*drug effects
MH  - Cells, Cultured
MH  - Cycloheximide/pharmacology
MH  - Cytoprotection/drug effects
MH  - Deferoxamine/antagonists & inhibitors/pharmacology
MH  - Drug Interactions
MH  - Enzyme Inhibitors/*pharmacology
MH  - Hydrogen Peroxide/antagonists & inhibitors/toxicity
MH  - Hydroxybenzoates/antagonists & inhibitors/pharmacology
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Indazoles/pharmacology
MH  - Mice
MH  - Oxidative Stress/*drug effects
MH  - Signal Transduction/drug effects
MH  - Vascular Endothelial Growth Factor A/*metabolism
EDAT- 2010/02/16 06:00
MHDA- 2010/06/23 06:00
CRDT- 2010/02/16 06:00
PHST- 2009/09/16 00:00 [received]
PHST- 2010/01/18 00:00 [revised]
PHST- 2010/02/02 00:00 [accepted]
PHST- 2010/02/16 06:00 [entrez]
PHST- 2010/02/16 06:00 [pubmed]
PHST- 2010/06/23 06:00 [medline]
AID - S0014-2999(10)00091-9 [pii]
AID - 10.1016/j.ejphar.2010.02.008 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2010 May 10;633(1-3):24-32. doi: 10.1016/j.ejphar.2010.02.008. 
      Epub 2010 Feb 11.