PMID- 25966950
OWN - NLM
STAT- MEDLINE
DCOM- 20151230
LR  - 20181202
IS  - 1559-7016 (Electronic)
IS  - 0271-678X (Print)
IS  - 0271-678X (Linking)
VI  - 35
IP  - 10
DP  - 2015 Oct
TI  - Inhibition of histone methyltransferases SUV39H1 and G9a leads to neuroprotection 
      in an in vitro model of cerebral ischemia.
PG  - 1640-7
LID - 10.1038/jcbfm.2015.99 [doi]
AB  - Cerebral ischemia induces a complex transcriptional response with global changes 
      in gene expression. It is essentially regulated by transcription factors as well 
      as epigenetic players. While it is well known that the inhibition of 
      transcriptionally repressive histone deacetylases leads to neuroprotection, the 
      role of histone methyltransferases in the postischemic transcriptional response 
      remains elusive. We investigated the effects of inhibition of the repressive H3K9 
      histone methyltransferases SUV39H1 and G9a on neuronal survival, H3K9 promoter 
      signatures and gene expression. Their inhibition either with the specific blocker 
      chaetocin or by use of RNA interference promoted neuronal survival in oxygen 
      glucose deprivation (OGD). Brain-derived neurotrophic factor (BDNF) was 
      upregulated and BDNF promoter regions showed an increase in histone marks 
      characteristic for active transcription. The BDNF blockade with K252a abrogated 
      the protective effect of chaetocin treatment. In conclusion, inhibition of 
      histone methyltransferases SUV39H1 and G9a confers neuroprotection in a model of 
      hypoxic metabolic stress, which is at least in part mediated by BDNF.
FAU - Schweizer, Sophie
AU  - Schweizer S
AD  - Department of Experimental Neurology, Charite - Universitatsmedizin Berlin, 
      Berlin, Germany.
FAU - Harms, Christoph
AU  - Harms C
AD  - Department of Experimental Neurology, Charite - Universitatsmedizin Berlin, 
      Berlin, Germany.
AD  - Center for Stroke Research Berlin, Charite - Universitatsmedizin Berlin, Berlin, 
      Germany.
FAU - Lerch, Heike
AU  - Lerch H
AD  - Department of Experimental Neurology, Charite - Universitatsmedizin Berlin, 
      Berlin, Germany.
AD  - NeuroCure Clinical Research Center, Charite - Universitatsmedizin Berlin, Berlin, 
      Germany.
FAU - Flynn, Jennifer
AU  - Flynn J
AD  - Department of Experimental Neurology, Charite - Universitatsmedizin Berlin, 
      Berlin, Germany.
FAU - Hecht, Jochen
AU  - Hecht J
AD  - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charite - 
      Universitatsmedizin Berlin, Berlin, Germany.
FAU - Yildirim, Ferah
AU  - Yildirim F
AD  - Department of Experimental Neurology, Charite - Universitatsmedizin Berlin, 
      Berlin, Germany.
AD  - NeuroCure Clinical Research Center, Charite - Universitatsmedizin Berlin, Berlin, 
      Germany.
FAU - Meisel, Andreas
AU  - Meisel A
AD  - Department of Experimental Neurology, Charite - Universitatsmedizin Berlin, 
      Berlin, Germany.
AD  - Center for Stroke Research Berlin, Charite - Universitatsmedizin Berlin, Berlin, 
      Germany.
AD  - NeuroCure Clinical Research Center, Charite - Universitatsmedizin Berlin, Berlin, 
      Germany.
FAU - Marschenz, Stefanie
AU  - Marschenz S
AD  - Department of Experimental Neurology, Charite - Universitatsmedizin Berlin, 
      Berlin, Germany.
AD  - NeuroCure Clinical Research Center, Charite - Universitatsmedizin Berlin, Berlin, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150513
PL  - United States
TA  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the 
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Isoenzymes)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Piperazines)
RN  - 28097-03-2 (chaetocin)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.1.1.- (Histone Methyltransferases)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/*drug therapy/*enzymology
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/pharmacology
MH  - Cell Count
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Cerebral Cortex/pathology
MH  - Female
MH  - Glucose/deficiency
MH  - Histone Methyltransferases
MH  - Histone-Lysine N-Methyltransferase/*antagonists & inhibitors
MH  - Hypoxia, Brain/pathology
MH  - Isoenzymes/antagonists & inhibitors
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Neuroprotective Agents/*therapeutic use
MH  - Piperazines/therapeutic use
MH  - Pregnancy
MH  - RNA Interference
MH  - Rats
MH  - Rats, Wistar
PMC - PMC4640311
EDAT- 2015/05/15 06:00
MHDA- 2015/12/31 06:00
PMCR- 2016/10/01
CRDT- 2015/05/14 06:00
PHST- 2015/02/03 00:00 [received]
PHST- 2015/04/13 00:00 [revised]
PHST- 2015/04/17 00:00 [accepted]
PHST- 2015/05/14 06:00 [entrez]
PHST- 2015/05/15 06:00 [pubmed]
PHST- 2015/12/31 06:00 [medline]
PHST- 2016/10/01 00:00 [pmc-release]
AID - jcbfm201599 [pii]
AID - 10.1038/jcbfm.2015.99 [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 2015 Oct;35(10):1640-7. doi: 10.1038/jcbfm.2015.99. 
      Epub 2015 May 13.