Low dose Hsp90 inhibitor 17AAG protects neural progenitor cells from ischemia induced death

Eric Bradley, Xiaying Zhao, Rebecca Wang, Darrell W Brann, Erhard Bieberich, Guanghu Wang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Stress adaptation effect provides cell protection against ischemia induced apoptosis. Whether this mechanism prevents other types of cell death in stroke is not well studied. This is an important question for regenerative medicine to treat stroke since other types of cell death such as necrosis are also prominent in the stroke brain apart from apoptosis. We report here that treatment with 17-N-Allylamino-17-demethoxygeldanamycin (17AAG), an Hsp90 inhibitor, protected neural progenitor cells (NPCs) against oxygen glucose deprivation (OGD) induced cell death in a dose dependent fashion. Cell death assays indicated that 17AAG not only ameliorated apoptosis, but also necrosis mediated by OGD. This NPC protection was confirmed by exposing cells to oxidative stress, a major stress signal prevalent in the stroke brain. Mechanistic studies demonstrated that 17AAG activated PI3K/Akt and MAPK cell protective pathways. More interestingly, these two pathways were activated in vivo by 17AAG and 17AAG treatment reduced infarct volume in a middle cerebral artery occlusion (MCAO) stroke model. These data suggest that 17AAG protects cells against major cell death pathways and thus might be used as a pharmacological conditioning agent for regenerative medicine for stroke.

Original languageEnglish (US)
Pages (from-to)353-362
Number of pages10
JournalJournal of Cell Communication and Signaling
Volume8
Issue number4
DOIs
StatePublished - Dec 30 2014

Fingerprint

tanespimycin
Cell death
Stem Cells
Ischemia
Cell Death
Stroke
Apoptosis
Regenerative Medicine
Cytoprotection
Middle Cerebral Artery Infarction
Brain
Oxygen
Necrosis
Glucose
Oxidative stress
Phosphatidylinositol 3-Kinases
Assays
Oxidative Stress
Pharmacology

Keywords

  • 17AAG
  • Hormesis
  • Hsp90
  • Ischemia
  • Regenerative and reparative medicine
  • Stress adaptation
  • Stroke

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Low dose Hsp90 inhibitor 17AAG protects neural progenitor cells from ischemia induced death. / Bradley, Eric; Zhao, Xiaying; Wang, Rebecca; Brann, Darrell W; Bieberich, Erhard; Wang, Guanghu.

In: Journal of Cell Communication and Signaling, Vol. 8, No. 4, 30.12.2014, p. 353-362.

Research output: Contribution to journalArticle

Bradley, Eric ; Zhao, Xiaying ; Wang, Rebecca ; Brann, Darrell W ; Bieberich, Erhard ; Wang, Guanghu. / Low dose Hsp90 inhibitor 17AAG protects neural progenitor cells from ischemia induced death. In: Journal of Cell Communication and Signaling. 2014 ; Vol. 8, No. 4. pp. 353-362.
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