Antiapoptotic and anti-inflammatory mechanisms of heat-shock protein protection

Midori A. Yenari, Jialing Liu, Zhen Zheng, Zinaida S. Vexler, Jongeun Lee, Rona G. Giffard

Research output: Contribution to journalArticle

220 Citations (Scopus)

Abstract

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. Overespressing 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.

Original languageEnglish
Pages (from-to)74-83
Number of pages10
JournalAnnals of the New York Academy of Sciences
Volume1053
DOIs
Publication statusPublished - 2005 Jan 1

Fingerprint

Heat-Shock Proteins
Anti-Inflammatory Agents
Stroke
Cell death
Brain
Neurodegenerative diseases
Gene transfer
Protein folding
HSP70 Heat-Shock Proteins
Matrix Metalloproteinases
Transgenic Mice
Neurons
Cell Death
Agglomeration
Chemical activation
Apoptosis
Protein Folding
Brain Ischemia
Astrocytes
Neurodegenerative Diseases

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Yenari, Midori A. ; Liu, Jialing ; Zheng, Zhen ; Vexler, Zinaida S. ; Lee, Jongeun ; Giffard, Rona G. / Antiapoptotic and anti-inflammatory mechanisms of heat-shock protein protection. In: Annals of the New York Academy of Sciences. 2005 ; Vol. 1053. pp. 74-83.
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Antiapoptotic and anti-inflammatory mechanisms of heat-shock protein protection. / Yenari, Midori A.; Liu, Jialing; Zheng, Zhen; Vexler, Zinaida S.; Lee, Jongeun; Giffard, Rona G.

In: Annals of the New York Academy of Sciences, Vol. 1053, 01.01.2005, p. 74-83.

Research output: Contribution to journalArticle

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