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Differential Neuroprotection from Human Heat Shock Protein 70 Overexpression in in Vitro and in Vivo Models of Ischemia and Ischemia-like Conditions

 Jong Eun Lee  ;  Midori A. Yenari  ;  Guo Hua Sun  ;  Lijun Xu  ;  Michelle R. Emond  ;  Danye Cheng  ;  Gary K. Steinberg  ;  Rona G. Giffard 
 EXPERIMENTAL NEUROLOGY, Vol.170(1) : 129-139, 2001 
Journal Title
Issue Date
Animals ; Astrocytes/cytology ; Astrocytes/drug effects ; Astrocytes/metabolism ; Brain Ischemia/metabolism* ; Cells, Cultured ; Dose-Response Relationship, Drug ; Genotype ; Glucose/deficiency ; Glucose/metabolism ; Glutathione/metabolism ; HSP70 Heat-Shock Proteins/biosynthesis* ; HSP70 Heat-Shock Proteins/genetics ; HSP70 Heat-Shock Proteins/pharmacology ; HeLa Cells ; Hippocampus/metabolism ; Hippocampus/pathology ; Humans ; Hydrogen Peroxide/pharmacology ; Hypoglycemia/metabolism ; Hypoxia, Brain/metabolism ; Male ; Mice ; Mice, Transgenic ; Neuronal Plasticity/genetics ; Oxidants/pharmacology ; Polymerase Chain Reaction
heat shock protein 70 ; stress response ; oxidative stress ; transgenic mouse ; cerebral ischemia
We previously showed that overexpressing the 70-kDa inducible heat shock protein in primary astrocyte cultures and in a rodent stroke model using viral vectors resulted in protection from ischemia and ischemia-like injury. However, viral transfection could potentially provoke a stress response itself; therefore, we examined whether transgenic mice constitutively expressing human heat shock protein 70 were protected from ischemic insults. Astrocyte cultures from brains of heat shock protein 70 transgenic mice were resistant to hydrogen peroxide injury in a dose-dependent fashion, but were less resistant to hypoglycemia and oxygen-glucose deprivation. Because hydrogen peroxide exposure and glucose deprivation are partially dependent on glutathione levels, we determined whether heat shock protein 70 transgenic cultures had altered glutathione levels under normal growth conditions. However, there was no significant difference in glutathione levels between heat shock protein 70 transgenic and wildtype astrocytes. Hippocampal, but not cortical neuron cultures from these same transgenic mice were also protected against oxygen-glucose deprivation and glutamate toxicity. In an in vivo model of permanent focal cerebral ischemia, there was no significant difference in infarct size assessed 24 h postinsult. These results suggest that heat shock protein 70 protects against some but not all kinds of central nervous system injury. The protective effects may be related to the nature and severity of the insults, as well as subpopulations of brain cells and dose-dependent effects of HSP70 overexpression.
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1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
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