C-terminus of heat shock cognate 70 interacting protein increases following stroke and impairs survival against acute oxidative stress

Jeannette N. Stankowski, Stephanie L H Zeiger, Evan L. Cohen, Donald B. Defranco, Jiyang Cai, Bethann McLaughlin

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The decision to remove or refold oxidized, denatured, or misfolded proteins by heat shock protein 70 and its binding partners is critical to determine cell fate under pathophysiological conditions. Overexpression of the ubiquitin ligase C-terminus of HSC70 interacting protein (CHIP) can compensate for failure of other ubiquitin ligases and enhance protein turnover and survival under chronic neurological stress. The ability of CHIP to alter cell fate after acute neurological injury has not been assessed. Using postmortem human tissue samples, we provide the first evidence that cortical CHIP expression is increased after ischemic stroke. Oxygen glucose deprivation in vitro led to rapid protein oxidation, antioxidant depletion, proteasome dysfunction, and a significant increase in CHIP expression. To determine if CHIP upregulation enhances neural survival, we overexpressed CHIP in vitro and evaluated cell fate 24h after acute oxidative stress. Surprisingly, CHIP overexpressing cells fared worse against oxidative injury, accumulated more ubiquitinated and oxidized proteins, and experienced decreased proteasome activity. Conversely, using small interfering RNA to decrease CHIP expression in primary neuronal cultures improved survival after oxidative stress, suggesting that increases in CHIP observed after stroke like injuries are likely correlated with diminished survival and may negatively impact the neuroprotective potential of heat shock protein 70.

Original languageEnglish (US)
Pages (from-to)1787-1801
Number of pages15
JournalAntioxidants and Redox Signaling
Volume14
Issue number10
DOIs
StatePublished - May 15 2011
Externally publishedYes

Fingerprint

HSC70 Heat-Shock Proteins
Oxidative stress
Oxidative Stress
Stroke
Survival
Proteins
HSP70 Heat-Shock Proteins
Proteasome Endopeptidase Complex
Ligases
Ubiquitin
Wounds and Injuries
Ubiquitin C
Hot Temperature
Ubiquitinated Proteins
Ubiquitin-Protein Ligases
Small Interfering RNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

C-terminus of heat shock cognate 70 interacting protein increases following stroke and impairs survival against acute oxidative stress. / Stankowski, Jeannette N.; Zeiger, Stephanie L H; Cohen, Evan L.; Defranco, Donald B.; Cai, Jiyang; McLaughlin, Bethann.

In: Antioxidants and Redox Signaling, Vol. 14, No. 10, 15.05.2011, p. 1787-1801.

Research output: Contribution to journalArticle

Stankowski, Jeannette N. ; Zeiger, Stephanie L H ; Cohen, Evan L. ; Defranco, Donald B. ; Cai, Jiyang ; McLaughlin, Bethann. / C-terminus of heat shock cognate 70 interacting protein increases following stroke and impairs survival against acute oxidative stress. In: Antioxidants and Redox Signaling. 2011 ; Vol. 14, No. 10. pp. 1787-1801.
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