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

Stankowski JN, Zeiger SL, Cohen EL, DeFranco DB, Cai J, McLaughlin B
Antioxid Redox Signal. 2011 14 (10): 1787-801

PMID: 20677910 · PMCID: PMC3078511 · DOI:10.1089/ars.2010.3300

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 24 h 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.

MeSH Terms (15)

Animals Cell Line, Tumor Cells, Cultured Chromatin Immunoprecipitation Chromatography, High Pressure Liquid Fluorescent Antibody Technique Glutathione Glutathione Disulfide Immunoblotting Mice Oxidative Stress Rats Rats, Sprague-Dawley Stroke Ubiquitin-Protein Ligases

Connections (1)

This publication is referenced by other Labnodes entities:

Links