0 340

Cited 12 times in

Heparin Inhibits NF-κB Activation and Increases Cell Death in Cerebral Endothelial Cells after Oxygen-Glucose Deprivation

Authors
 Jeong Ho Lee  ;  Jinu Lee  ;  Gi Ho Seo  ;  Chul Hoon Kim  ;  Young Soo Ahn 
Citation
 JOURNAL OF MOLECULAR NEUROSCIENCE, Vol.32(2) : 145-154, 2007 
Journal Title
 JOURNAL OF MOLECULAR NEUROSCIENCE 
ISSN
 0895-8696 
Issue Date
2007
MeSH
Animals ; Brain Neoplasms ; Cell Death/drug effects* ; Cell Line ; Cell Nucleus/drug effects ; Cell Nucleus/physiology ; Cerebrovascular Circulation/drug effects ; Cerebrovascular Circulation/physiology* ; Consensus Sequence ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/physiology* ; Genes, Reporter ; Glucose/deficiency* ; Heparin/pharmacology* ; Hypoxia/physiopathology* ; Mice ; NF-kappa B/drug effects ; NF-kappa B/genetics ; NF-kappa B/physiology* ; Polymerase Chain Reaction ; Transfection
Abstract
Heparin is a classic anticoagulant that is commonly used in the treatment of acute ischemic stroke (AIS). Its use remains controversial, however, due to the risk of cerebral hemorrhagic transformation. In addition to anticoagulant effects, diverse effects on transcription factors can be caused by heparin. Among the transcription factors potentially affected is nuclear factor kappa B (NF-κB), a protein that is reportedly related to the survival of cerebral endothelial cells. We investigated the effect of heparin on NF-κB activation and cell death following oxygen-glucose deprivation (OGD), an experimental model of AIS. We subjected bEnd.3 cells from a murine cerebral microvascular endothelial cell line to OGD. We examined the effect of heparin on OGD-induced NF-κB activation and its mechanism of action, using electrophoretic mobility shift assays, reporter gene analysis, real-time RT-PCR, Western blot analysis, and confocal microscopy. We also measured the effect of heparin on OGD-induced cell death using an MTT assay. Heparin inhibited both tumor necrosis factor α- and OGD-induced NF-κB activation. Heparin was taken up by endocytosis and then entered the nucleus. Heparin did not affect the nuclear translocation of NF-κB, but instead inhibited the DNA binding of NF-κB in the nucleus. Cells were more susceptible to OGD-induced cell death after heparin treatment. Besides producing an anticoagulation effect, heparin also inhibits NF-κB activation, resulting in increased susceptibility to OGD-induced cell death. This effect may be responsible for hemorrhagic transformation in patients following heparin treatment for AIS.
Full Text
http://link.springer.com/article/10.1007/s12031-007-0026-3
DOI
10.1007/s12031-007-0026-3
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Ahn, Young Soo(안영수)
Lee, Jeong Ho(이정호)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96485
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links