Heat shock induces IkappaB-alpha and prevents stress-induced endothelial cell apoptosis.
| Autor: | DeMeester SL; Department of Surgery, Washington University School of Medicine, St Louis, Mo, USA., Buchman TG, Qiu Y, Jacob AK, Dunnigan K, Hotchkiss RS, Karl I, Cobb JP |
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| Jazyk: | angličtina |
| Zdroj: | Archives of surgery (Chicago, Ill. : 1960) [Arch Surg] 1997 Dec; Vol. 132 (12), pp. 1283-7; discussion 1287-8. |
| DOI: | 10.1001/archsurg.1997.01430360029005 |
| Abstrakt: | 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 alpha 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 micromol/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 uptake and staining with annexin V and propidium iodide, respectively. Inducible heat shock protein 70 and inhibitor kappa B alpha 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 micromol/L at 4 hours). Protection against apoptosis correlated with increased heat shock protein 70 and inhibitor kappa B alpha 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. |
| Databáze: | MEDLINE |
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