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Antiapoptotic and Anti‐inflammatory Mechanisms of Heat‐Shock Protein Protection
Author(s) -
YENARI MIDORI A.,
LIU JIALING,
ZHENG ZHEN,
VEXLER ZINAIDA S.,
LEE JONG EUN,
GIFFARD RONA G.
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2005.tb00012.x
Subject(s) - heat shock protein , hsp70 , apoptosis , inflammation , transgene , programmed cell death , genetically modified mouse , chaperone (clinical) , microbiology and biotechnology , neuroprotection , microglia , biology , cancer research , medicine , immunology , pharmacology , gene , pathology , biochemistry
A bstract : We and others have previously shown that heat‐shock proteins (HSPs) are involved in protecting the brain from a variety of insults including stroke, epilepsy, and other related insults. While the mechanism of this protection has largely been thought to be due to their chaperone functions (i.e., preventing abnormal protein folding or aggregation), recent work has shown that HSPs may also directly interfere with other cell death pathways such as apoptosis and inflammation. Using models of cerebral ischemic and ischemia‐like injury, we overexpressed the 70‐kDa heat‐shock protein (HSP70) using gene transfer or by studying a transgenic mouse model. HSP70 protected neurons and astrocytes from experimental stroke and stroke‐like insults. HSP70 transgenic mice also had better neurological scores following experimental stroke compared to their wild‐type littermates. Overexpressing HSP70 was associated with less apoptotic cell death and increased expression of the antiapoptotic protein, Bcl‐2. Furthermore, HSP70 suppressed microglial/monocyte activation following experimental stroke. HSP70 overexpression also led to the reduction of matrix metalloproteinases. We suggest that HSPs are capable of protecting brain cells from lethal insults through a variety of mechanisms and should be explored as a potential therapy against stroke and other neurodegenerative diseases.