Heat shock induces IκB-α and prevents stress-induced endothelial cell apoptosis

Susan L. DeMeester, Timothy G. Buchman, Yuyu Qiu, Ammini K. Jacob, Keith Dunnigan, Richard S. Hotchkiss, Irene Karl, J. Perren Cobb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Objective: To determine whether prior heat shock would attenuate endothelial cell apoptosis and whether any effect of preemptive heat shock is mediated through a nuclear factor kappa B and inhibitor kappa B α mechanism. Design: A randomized, controlled in vitro study. Setting: A laboratory in a large, academic medical center. Interventions: Cultured primary porcine endothelial cells were treated with increasing doses of sodium arsenite (40- 160 μmol/L), after which the interval until subsequent apoptotic (lipopolysaccharide-arsenite) challenge was varied (4-16 hours). The degree of cell death and apoptosis were determined using neutral red up-take and staining with annexin V and propidium iodide, respectively. Inducible heat shock protein 70 and inhibitor kappa B α levels in treated cells were determined by Western blot analysis. Lipopolysaccharide-induced nuclear factor kappa B activity was assessed using an electrophoretic mobility shift assay. Results: Prior arsenite treatment decreased cell death by apoptosis in a time- and dose-dependent manner. Specifically, a higher sodium arsenite concentration and shorter intervals afforded better protection (P=.01, 160 μmol/L at 4 hours). Protection against apoptosis correlated with increased heat shock protein 70 and inhibitor kappa B α levels and decreased nuclear factor kappa B binding activity. Conclusions: Arsenite, an inducer of the heat shock response, decreased stress-induced endothelial cell apoptosis. The mechanism of this protection may include decreased nuclear factor kappa B activity or increased inducible heat shock protein 70 levels. Heat shock protein 70 may serve as a molecular marker to determine not only the phenotypic state of the cell but also the durability of protection afforded by heat shock. These data support the hypothesis that stress-induced changes in transcription factor activity and protein expression can regulate the induction of apoptosis.

Original languageEnglish
Pages (from-to)1283-1288
Number of pages6
JournalArchives of Surgery
Issue number12
StatePublished - Dec 1997
Externally publishedYes


Dive into the research topics of 'Heat shock induces IκB-α and prevents stress-induced endothelial cell apoptosis'. Together they form a unique fingerprint.

Cite this