PMID- 20456012
OWN - NLM
STAT- MEDLINE
DCOM- 20100823
LR  - 20231213
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 114
IP  - 2
DP  - 2010 Jul
TI  - Possible involvement of DNA methylation in NKCC1 gene expression during postnatal 
      development and in response to ischemia.
PG  - 520-9
LID - 10.1111/j.1471-4159.2010.06772.x [doi]
AB  - In CNS, GABA(A) receptor-mediated responses switch from depolarization to 
      hyperpolarization during postnatal development. This switch is mediated by 
      developmental down-regulation of inwardly directed Na(+)-K(+)-2Cl(-) 
      co-transporter type 1 (NKCC1) and up-regulation of outwardly directed K(+)-Cl(-) 
      co-transporter type 2. While several factors have been shown to regulate 
      K(+)-Cl(-) co-transporter type 2 expression, little is known about the mechanisms 
      by which the expression of NKCC1 is regulated during postnatal development. Here, 
      we report a novel epigenetic mechanism underlying the developmental regulation of 
      NKCC1 gene expression in the rat cerebral cortex. In vitro DNA methylation of the 
      NKCC1 promoter region, which contains a high density of 
      cytosine-phosphodiester-guanine islands, significantly decreased the expression 
      of NKCC1 mRNA, and the degree of methylation of the NKCC1 promoter region 
      significantly increased during postnatal development. In addition, treatment with 
      5-aza-2'-deoxycytidine, a specific DNA methyltransferase inhibitor, elicited an 
      increase in the expression of NKCC1 mRNA and protein in cortical slice cultures. 
      Focal ischemic injury induced by the occlusion of the middle cerebral artery led 
      to the re-expression of NKCC1 mRNA and protein even in the mature rat cortex. The 
      re-expression of NKCC1 mRNA and protein in the injured cerebral cortex was 
      related to a decrease in the methylation status of the NKCC1 promoter region. Our 
      results indicate that epigenetic mechanisms, such as DNA methylation, might be 
      involved in the regulation of NKCC1 gene expression during postnatal development 
      as well as under pathological conditions.
FAU - Lee, Hae-Ahm
AU  - Lee HA
AD  - Department of Pharmacology, School of Dentistry, Kyungpook National University, 
      Daegu, Korea.
FAU - Hong, Su-Hyung
AU  - Hong SH
FAU - Kim, Jung-Wan
AU  - Kim JW
FAU - Jang, Il-Sung
AU  - Jang IS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100428
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Slc12a2 protein, rat)
RN  - 0 (Sodium-Potassium-Chloride Symporters)
RN  - 0 (Solute Carrier Family 12, Member 2)
RN  - 0 (Symporters)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Cerebral Cortex/growth & development/*metabolism
MH  - *DNA Methylation
MH  - Infarction, Middle Cerebral Artery/complications
MH  - Ischemic Attack, Transient/etiology/*metabolism
MH  - Molecular Sequence Data
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sodium-Potassium-Chloride Symporters/biosynthesis/*physiology
MH  - Solute Carrier Family 12, Member 2
MH  - Symporters/biosynthesis
MH  - K Cl- Cotransporters
EDAT- 2010/05/12 06:00
MHDA- 2010/08/24 06:00
CRDT- 2010/05/12 06:00
PHST- 2010/05/12 06:00 [entrez]
PHST- 2010/05/12 06:00 [pubmed]
PHST- 2010/08/24 06:00 [medline]
AID - JNC6772 [pii]
AID - 10.1111/j.1471-4159.2010.06772.x [doi]
PST - ppublish
SO  - J Neurochem. 2010 Jul;114(2):520-9. doi: 10.1111/j.1471-4159.2010.06772.x. Epub 
      2010 Apr 28.