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FasL shedding is reduced by hypothermia in experimental stroke

Authors
 Liping Liu  ;  Jong Youl Kim  ;  Maya A. Koike  ;  Yone Jung Yoon  ;  Xian Nan Tang  ;  Hualong Ma  ;  Hokyou Lee  ;  Gary K. Steinberg  ;  Jong Eun Lee  ;  Midori A. Yenari 
Citation
 JOURNAL OF NEUROCHEMISTRY, Vol.106(2) : 541-550, 2008 
Journal Title
JOURNAL OF NEUROCHEMISTRY
ISSN
 0022-3042 
Issue Date
2008
MeSH
Analysis of Variance ; Animals ; Caspase 8/metabolism ; Cells, Cultured ; Cerebral Cortex/cytology ; Disease Models, Animal ; Embryo, Mammalian ; Fas Ligand Protein/genetics ; Fas Ligand Protein/metabolism* ; Gene Expression Regulation/physiology* ; Glucose/deficiency ; Hypothermia, Induced/methods* ; Hypoxia ; Ischemia/therapy* ; Male ; Matrix Metalloproteinases/pharmacology ; Mice ; Mice, Inbred C57BL ; Neurons/drug effects ; Neurons/metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors ; fas Receptor/metabolism
Keywords
apoptosis ; cerebral ischemia ; Fas/Fa니 ; hypo-thermia ; matrix metalloproteinases ; stroke
Abstract
Protection by mild hypothermia has previously been associated with better mitochondrial preservation and suppression of the intrinsic apoptotic pathway. It is also known that the brain may undergo apoptotic death via extrinsic, or receptor-mediated pathways, such as that triggered by Fas/FasL. Male Sprague-Dawley rats subjected to 2 h middle cerebral artery occlusion with 2 h intraischemic mild hypothermia (33 degrees C) were assayed for Fas, FasL and caspase-8 expression. Ischemia increased Fas, but decreased FasL by approximately 50-60% at 6 and 24 h post-insult. Mild hypothermia significantly reduced expression of Fas and processed caspase-8 both by approximately 50%, but prevented ischemia-induced FasL decreases. Fractionation revealed that soluble/shed FasL (sFasL) was decreased by hypothermia, while membrane-bound FasL (mFasL) increased. To more directly assess the significance of the Fas/FasL pathway in ischemic stroke, primary neuron cultures were exposed to oxygen glucose deprivation. Since FasL is cleaved by matrix metalloproteinases (MMPs), and mild hypothermia decreases MMP expression, treatment with a pan-MMP inhibitor also decreased sFasL. Thus, mild hypothermia is associated with reduced Fas expression and caspase-8 activation. Hypothermia prevented total FasL decreases, and most of it remained membrane-bound. These findings reveal new observations regarding the effect of mild hypothermia on the Fas/FasL and MMP systems
Files in This Item:
T200801084.pdf Download
DOI
10.1111/j.1471-4159.2008.05411.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Youl(김종열) ORCID logo https://orcid.org/0000-0002-8340-2894
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/107358
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